Download Cell Membranes and Disease

Cell Membranes and Disease
Genes, Viruses, Hormones and the Immune Response—An Introduction
L E O N D M O C H O W S K I , M.B,
C H . B . , M.D.,
P H . D . , AND J A M E S M. B O W E N , P H . D .
The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute,
Texas Medical Center, Houston, Texas 77025
of cell membranes are intimately connected with cell
replication and cell organization. Both
replication and organization are outstanding features of living systems and both
are determined by the cell membranes. 6
They play an essential part in the life,
health and disease of cells and in turn
of the host that harbors the cells. They
are the very basis of coordination of
structure and function of the cells and in
turn of their host. Cell membranes have
different functions in different parts of the
cells depending on their location—that is,
surface or interior of the cells. Interest
in structure, function and replication of
cells has led to studies of the problems
associated with cell organization in health
and disease in its multifaceted aspects, including neoplasia. The cell membrane, now
known as the "plasma membrane," existed
in the old approach to a study of cells
as a barrier between the interior of the
cell and its surroundings. T h e cell membrane was considered a barrier controlling
exchange of material between the cytoplasm of a cell and its surroundings.
The knowledge that cellular substructures and the great variety of activities
S T R U C T U R E AND F U N C T I O N
Received October 29, 1974; accepted for publication December 9, 1974.
Supported in part by Grants CA-05831 and RR05511 from the National Cancer Institute, NIH,
USPHS.
Key words: Cell membranes and disease; Genes;
Viruses; Hormones; Immune response.
Reprints of this entire Research Symposium are
available from the ASCP Meeting Services Department, 2100 West Harrison Street, Chicago, Illinois
60612, for $3.00 per copy.
and interactions they undergo are enclosed
in a membrane has existed since the middle
of the last century. During many of the
intervening years, however, this limiting
cellular membrane was viewed as a kind
of semipermeable bag that contained cellular activities with only little participation
in them. Within the past two decades,
morphologic studies have revealed that not
only the entire cell but also many subcellular organelles are enclosed by and/or
associated with structurally and functionally highly complex membrane structures
with many common and some quite distinctive features.
The initial studies led to the compilation of morphologic and chemical data to
produce a model of the cell membrane
as a semipermeable and osmotically sensitive, but rather rigid and static, structure
composed of lipid, protein, and carbohydrate in a matrix or laminar arrangement.
During the past few years, however, rapidly
developing knowledge in a number of different disciplines has brought the cell membrane as a functional organelle into sharp
focus and has made necessary an extensive reappraisal of earlier models of membrane structure and organization.
These new findings have necessitated
a formulation of a cell membrane model
compatible with dynamic behavior and active participation in multiple intra- and
intercellular functions. Thus, the complex
dynamics of cell contact-induced inhibition
of cell growth, division, and movement,
intercellular communication, regulatory
actions of hormones and small molecular
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DMOCHOWSKI AND BOWEN
mediators, and the great variety of antigenic specificities of intact cells must be
taken into consideration in any view of
cell membrane structure.
Electron microscopy, with its refinements of cell fixation, embedding, and thin
sectioning of cells, provided information
not only revealing but most important in
its implications pertaining to cell structure
and function in health and disease of the
host. Electron microscopy demonstrated
the internal structure of cell boundaries,
that is, plasma membranes and the structures of membranes of submicroscopic
elements of cells such as mitochondria,
endoplasmic reticulum, and the Golgi zone.
Electron microscopy has also demonstrated
that all these submicroscopic structures are
associated with membranes, all of which
form an integrated system with each
other and with the plasma membrane of
cells of both animals and humans.
New approaches and new technics have
led to the acquisition of new knowledge
of the structure of cell membranes and
of the organization and interaction of their
components. Application of many technics,
some old but improved and some entirely new, has led to our present understanding of the structure of cell membranes, of their interaction, of the part
played by them in immune response to
various factors, including viruses, and
of their behavior, both structural and functional, in abnormal growth processes,
including neoplasia.
Many technics, such as x-ray diffraction,
spectroscopy, electron microscopy, immunoelectron microscopy, biological methods including the widest possible range
comprising tissue culture, physiology, biochemistry and many others, have led to
our present understanding of the structure and function of cell membranes.
While this knowledge is far from complete,
it has led to our better understanding of
the behavior and interaction of cells forming the basis of the beginning of our
A.J.C.P.—Vol.
63
knowledge of the reaction of the host
as directed by genetic, hormonal, and various external environmental factors to
various disease processes, including neoplasia.
Cell membranes are known to be composed of structural protein with attached
lipids, associated enzymes, and a polysaccharide coat.22 Changes in properties of any
of the membranes due to any of the
multiplicity of factors may lead to a
change of the properties and function of
other membranes and result in many abnormalities of the host. Alteration in the
metabolism of any one of the components
of cell membranes, for example lipids,
may be due to heredity or genes, hormones or viruses. Abnormalities in cell
membranes due to hereditary defects in
lipid metabolism, indicated in abnormalities of renal function, are known to be
associated with a number of clinical states
such as Franconi syndrome, cystic fibrosis
of the pancreas, renal glycosuria, and
others. 22
Membrane abnormalities in which enzymes of lipid metabolism are involved
include such disorders as Gaucher's disease, Nieman-Pick disease, and Tay-Sachs
disease. Conditions proved to be related
to changes in membrane components are
due to hereditary defects in lipid metabolism.22 Phospholipids and glycolipids are
components of at least some cell membranes that have different lipid class compositions. This may indicate the complexity of the bases of various disease
syndromes.
Lipids are one of the constituents of
cell membranes present in high concentration, but their roles in some specific
but not yet specified functions remain
to be investigated. 17 The results of x-ray
diffraction studies have indicated that
there exists a large variety of structures
of the lipid-water systems. Structures involving lipids are known to be very labile.
Therefore, only with special care being
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INTRODUCTION: CELL MEMBRANES AND DISEASE
taken, electron microscopy has been able
to reveal some phases of their structure,
in spite of their widespread occurrence.
There appears to exist at least some correlation between structure and function of
biological membranes, as revealed by x-ray
diffraction studies of lipid-water systems. 17
However, even the x-ray diffraction technic
is limited in its application to study of
the complex structure and function of
cell membranes. There is no doubt that
in order to solve at least some of the
present-day problems of cell membranes,
the use of a number of physical, chemical
and biochemical technics is needed, as well
as an interdisciplinary approach. Such an
approach is needed because of the lack
of knowledge of what indeed a cell membrane is, the incomplete knowledge of the
various components of cell membranes,
and last, but not least, the realization of
the existence of dynamic rather than
static conditions of the structure of cell
membranes. 8 Progress has been made,
however, in our knowledge of cell membranes, through the applications of physics
and physical chemistry and the use of
physical technics (spectroscopy, optical
rotary dispersion, x-rays).
T h e interaction of drugs, vitamins, hormones, viruses can be studied by using
physical methods already described and by
the use of various biological technics.
Many of the activities of cells occur within
and through membranes, resulting in cellular organization being a function of cell
membranes. 8 Interest in the structure and
function of membranes is even greater
today than ever before. It appears, however, that we are only at the beginning
of our understanding of cell membranes,
their structure, function, and interrelationship, which are of basic importance in the
life of cells and their relationship within
a host.
Recent years have seen an impressive
growth of interest in cellular membranes
shared by physiologists, physicists, bio-
621
chemists, biologists, chemists, and physicians. 7 There are ever-increasing signs of
attempts to bridge the gap between the
physical and biomedical aspects of studies
of cellular membranes which have already
led to better understanding of the dynamics of cell membranes, their behavior
under hormonal influence, their activity
in viral infections, and their participation
in the development of membranes of virus
particles. T h e roles of plasma membrane
in immunologic reactions of the host and
in transformation to malignant processes
are other aspects not only of interest but of
far-reaching importance in an understanding of the reaction of the host to an injury,
to an infection, and to the neoplastic process.
Viruses have only recently been recognized as important tools in cell membrane
research. 16 T h e internal component of
many viruses, composed of nucleic acid
and protein, is surrounded by an envelope
which resembles cellular membranes and in
the electron microscope appears as the
so-called "unit membrane." T h e envelope
of viruses resembles cellular membranes,
is comprised morphologically of a unit
membrane structure and chemically of proteins, lipids, and carbohydrates. This envelope contains virus-specific proteins, and
the nature of host antigens in the viral
envelope has not yet been resolved. 16
Envelope polypeptides of at least some
viruses are encoded in the viral genome.
Although viruses may use the cell plasma
membrane during their formation, no host
protein appears to be incorporated in the
virus particles or virions. However, in some
other viruses such as the oncogenic viruses,
herpes and poxviruses, their complex polypeptide composition does not allow, at
present, any conclusion regarding whether
the host proteins are an integral part of
the virus particles or are contaminants.
Glycoproteins are constituents of the membrane of the so-called "enveloped viruses"
and thus have a similarity to cell membranes.
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DMOCHOWSKI AND BOWEN
During the past few years, studies have
been carried out on the arrangement of
proteins, lipids, and carbohydrates in viral
envelopes or membranes. Physical and
chemical technics and electron microscopy
have greatly contributed to our knowledge of the structure of viral envelopes,
composed of surface projections, a central
layer with the trilaminar appearance of a
unit membrane and an additional inner
leaflet not present in all viruses. 16 The
differences of interaction of concanavalin
A and of phytoagglutinin depending on
the presence or absence of spikes in the
envelope of virions have provided evidence of the presence of glycoproteins in
the spikes and the presence of the glycolipids in a separate lipid layer.16
A considerable amount of study has
been carried out on the viral envelope
structure and the biogenesis of viral envelopes. 16 T h e results indicate that viral
envelopes and cellular membranes have
many common features in morphologic
appearance and chemical composition.
The envelope of at least some viruses
consists of a central lipid bilayer with the
inner surface composed of a protein layer
and an outer layer covered by glycoprotein spikes. T h e viral envelope, with its
simple protein pattern, is of great help
in studies of the assembly of the envelope
and the interactions of proteins and lipids.
Thus, it represents an additional basis for
study of membrane structure, biogenesis,
and reaction of cells to internal and external factors that may lead to diseases
of various types, including neoplasia. 16
Many hormonal effects can be ascribed
to changes in cellular function induced
by the hormone. 2 During the past few
years, considerable progress has been
achieved in our understanding of the
molecular basis of cellular responses to
some hormones. Demonstration by E. W.
Sutherland and T. W. Roll26 that the
adenylate cyclase system in mammalian
liver cells functions as the effector system
A.J.C.P.—Vol.
63
for glucogen and epinephrine has been of
far-reaching importance. Both hormones
stimulate the activity of adenylate cyclase,
and increased intracellular concentration
of cyclic 3',5'-adenosine monophosphate
(cyclic AMP), a product of this enzyme,
leads to most of the known actions of
these hormones in the liver.20
A second major insight into the molecular basis of cellular responses resulted
from the demonstration that the plasma
membrane of the target cells contains both
the recognition system and effector system for the peptide hormones. 2 As a result,
however, of rapid progress in the study
of hormonal action from the cellular to
the subcellular and even the molecular
level, alterations in cellular function produced by polypeptide hormones have been
studied in terms of a three-component
system.2 T h e system is composed of the
receptor, which recognizes the hormone;
the effector, which in turn mediates alterations in cellular function; and the transducer, which couples the receptor to the
effector. These three components are referred to as the initiator system for peptide hormone activity.2 They are the plasma
membrane constituents involved from the
initial contact of the cell with a peptide
hormone through activation of the processes that mediate the effects of the hormone. Thus the primary site of peptide
hormone action is the plasma membrane
of the target cell. Isolation, structural
characterization of these components, and
understanding of their interaction will be
of great importance to all interested in
biological membranes, their functions, and
the relationship of these functions to membrane structure.
The part played by plasma membrane
in the process of malignancy, invasiveness, and metastasis was recognized long
ago. 30 There is a great deal of evidence
that neoplasia comprises changes in which
the plasma membrane has been critically
altered. According to the hypothesis of
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INTRODUCTION: CELL MEMBRANES AND DISEASE
Wallach, 30 oncogenic agents alter the
cooperative properties of cellular membranes, modifying numerous membrane
functions, and lead to pleomorphic
changes present in neoplasia. The presence of an abnormal structural component
in plasma membrane may lead to morphologic changes, appearance of new antigenicity, change in permeability, and
alteration in the function of membraneassociated enzymes.
T h e interaction of malignant cells is
defective, and lack of contact inhibition
is much less prominent in neoplastic than
in normal cells. It appears to represent
an important regulatory mechanism. Cell
fusion produced by myxoviruses and by
some oncogenic viruses represents an extreme form of cell contact, and may parallel
malignancy. 30
Immunologic changes appear to be
genetically best defined as plasma membrane alterations of the neoplastic state.
Plasma membranes of tumor cells induced
by chemical, physical, and viral carcinogens
contain tumor antigens not present in the
tissues of origin. 5,15 T h e new tumor antigens play an important part in the t u m o r host relationship and may result in immunologic elimination of the malignant
cells. It is now well known that in chemically
induced tumors the new antigens appear
tumor-specific, and tumors induced by a
virus have the same new transplantation
antigens irrespective of the tissue or species
of origin. Neoplastic transformation of cultured hamster cells by various oncogenic
factors results in the appearance of
Forssman antigen on the surface of altered
cells.29 This glycolipid antigen present in
embryonic hamster cells has been demonstrated in tumors of the human gastrointestinal tract. 12,13 A radioimmunoassay
for circulating carcinoembryonic gastrointestinal antigens has been developed 27 and
is now being used in diagnosis of cancer
of the colon. Extensive studies of the distribution of carcinoembryonic antigens in
623
many types of neoplasia and other diseases
are now being conducted.
Neoplastic change often results in deletion of certain organ-specific antigens. 1
It is now known that neoplastic conversion changes proteins of the plasma membrane of the transformed cells, resulting
in altered agglutinability of the cells.30
Pleiotropic membrane alterations in cancer
cells appear to include changes in the transport of critical metabolites, thus giving selective advantage to the neoplastic cells.30
The immune response involves the
plasma membrane of cells as carrier of
specific groups of surface topography, distinguishing self from not-self, tissue from
tissue, various stages of differentiation and
diverse surface parts of a given same
cells.30 T h e immune response involves the
plasma membrane in immunocytes responsible for initiation of immune responses;
plasma membrane acts as catalytic surface
for the generation of complement, and as
a target of immunologic cell killing.30
Cell-mediated cytotoxicity is not yet
properly understood in terms of cell membrane-mediated processes. 19 In cell-mediated cytotoxicity, lymphocytes and membranes of target cells fuse and form cytoplasmic bridges. It remains to be ascertained whether such contacts are essential
for cell-mediated immunity. 30
T h e roles played by the plasma membrane in health and disease cannot be
left without a mention of its part in fertility. T h e penetration of the sperm
through the plasma membrane of the ovum
is a major world health problem. Its understanding may offer means for regulation
of population growth. 30
Although cell membranes play a most
important part in cellular phenomena,
our knowledge of molecular structure and
in turn function of the membranes is
still in its beginning. Singer and Nicholson 25 have presented a fluid mosaic model
for organization and structure of proteins
and lipids of biological membranes and
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DMOCHOWSKI AND BOWEN
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the resulting functions and phenomena and within the cell by response and conof these membranes. Rothschild and Stan- trol of its membranes.
ley21 have proposed that certain membrane
It appears that a great deal of informaproteins embedded in the lipid bilayer tion on the cell surface will come from
are responsible for ionic transport through study of lymphocytes and their interacthe membrane, and are similar in struc- tion with mitogens. 10 The cell membrane
ture and function to certain enzymes.
acts as a growth control system through
A great deal of research on immuno- control of molecular transport, probably
genetics of cell surfaces has been centered controlled by the cyclic nucleotide levels,
on the relation of cell surface antigens which are often correlated with growth
10
to the transplantability of tissues and properties of cells of certain types. Cyclic
organs, differential cell surface structure nucleotides may act as internal messengers
and cellular differentiation, and the rela- in growth and in other regulatory sys10
tionship of cell surface antigens to leu- tems in the cell. Cyclic AMP may act
through protein phosphorylation, shown
kemia virus genomes. 4
Isolation and purification of glycopro- to be modified in lymphocytes after stimteins from cell membranes of human ulation of growth.
tumors such as carcinoma of the breast,
Changes in the architecture of cell sursarcoma, and some others, in view of the face occur in many chemically induced
demonstration of antibodies to the tumors tumors, which in turn result in the appearin sera of patients with these neoplastic ance of new cell-surface antigens, some of
diseases, may lead to demonstration of anti- which are specific components of the tumor
genic determinants for the tumors. If cell and others, products of re-expressed
different tumors have tumor-specific anti- fetal genes. 3 T h e appearance of neoantigens, it may be possible to design specific gens may be accompanied by the deleimmunologic tests for detection of these tion (or masking) of cell-surface antigens.
tumors and to manage these tumors by Biochemical characterization of tumoraugmentation of the immune responses of associated antigens is now possible. This
the patients.
should lead to the development of imIt remains to be seen to what extent munologic assays for study of the biostudies of cell changes induced by RNA synthesis of tumor-associated antigens. Imand DNA tumor viruses linking patho- munoelectron microscopy already is able
genic, immunologic, and transforming to provide accurate methods for localizamechanisms will lead to understanding of tion of antigens within certain regions of
growth control in mammalian cells and the the cell surface. These developments will
biochemical differences between normal make possible the analysis of changes in
and neoplastic cells. This knowledge, in the cell surface during chemical as well
3
turn, could result in better treatment and as viral carcinogenesis.
possible prevention of cancer.
During the past few years, evidence has
Literature on cell membranes, their or- accumulated about the relationship of cerganization, structure, their part in cell tain properties of the cell surface, such
growth, transformation, differentiation, as contact inhibition, intercellular linkages
and cell interaction is accumulating at a and antigenicity of cells, to the structure
great rate. 9,10 ' 18 T h e behavior of a cell is and function of membrane-bound glycodetermined by the response of its surface lipid or glycoprotein and their related enmembranes to incoming signals and their zymes. 14 Molecular changes of cell memtransmission to the interior of the cell branes associated with malignant trans-
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INTRODUCTION: CELL MEMBRANES AND DISEASE
formation, physical and chemical, have
been described, although none has yet been
successfully correlated with characteristic
biological properties of tumor cells.14
Nevertheless, some of these molecular
changes are essential steps in the process
of malignant transformation of cells, as
some of them can be reversed when the
biological properties of tumor cells transformed by a temperature-sensitive mutant
of oncogenic viruses are reversed to a normal state at nonpermissive temperature. 1 4
Two types of membrane changes involving glycoprotein and glycolipids have
been established as associated with malignant transformation: enhanced agglutinability of cells by some agglutinins and
blocked synthesis of ganglioside, neutral
glycolipids and some glycoprotein carbohydrates. 14 Enhanced agglutinability has
been observed in cells transformed by DNA
viruses, but evidence for RNA viruses is
rather limited. 14 Glycolipid or sialosylglycopeptide synthesis is closely associated
with transformation and can be reversed
with reversion of malignancy. 14 Understanding of the cell membrane processes
mediated via glycolipid may well be one
of the keys to our understanding of the
secrets of neoplasia. 27
Cyclic adenosyl monophosphate (cyclic
AMP) has been implicated in the restoration of normal properties to transformed
cells, which contain less cyclic AMP than
nontransformed cells. Treatment with
cyclic AMP affects cell morphology, growth
rate, and density of transformed cells.
Agglutination of cells by plant lectins,
a property associated with transformed
cells, is decreased by treatment with cyclic
AMP. Treatment of Chinese hamster ovary
cells with dibutyryl cyclic AMP has recently been shown to lead to formation
of large numbers of particles that contain 70S RNA and RNA-directed DNA
polymerase, properties characteristic of
RNA tumor viruses. 28 Associated with par-
625
ticle production is a cell-surface change reflected by a large increase in cell agglutinability. Both these properties are reversible
when the cells are grown in the absence of
cyclic AMP. 28
It is now known that morphologic expression of cell transformation and the
surface changes associated with increased
cell agglutination are controlled by the expression of different sarcoma genes. 23
Non-virus-producing cells transformed by
murine sarcoma virus are agglutinated by
concanavalin A to the same level as normal corresponding cells (NIH/3T3). Infection with the murine leukemia virus
greatly increases the agglutination of transformed cells, but not that of normal cells.23
A gradual increase of a specific group
of glucose-containing glycopeptides of cellsurface membranes has been shown to correlate with gradual acquisition of the transformed phenotype of hamster cells showing delayed transformation by polyoma,
a DNA virus. 11 T h e amount of these glycopeptides appears to be representative
of an increase in monnose, galactose,
and sialic acid. Thus, it appears that specific
changes in surface membrane glycopeptides are associated with tumorigenesis.
These findings suggest that specific surface membrane glycopeptides accompany
viral transformation and tumorigenesis. 11
In the case of another DNA virus, the
vaccinia virus infection of cells (HeLa),
synthesis of plasma membrane proteins
and glycoproteins different from those
present in the uninfected host takes place.31
The plasma membrane changes induced
by vaccinia infection differ from those
produced by the so-called "budding viruses" in that in the latter case both host
components and newly synthesized virusinduced non-virion components coexist in
the plasma membrane of cells.31
Perhaps the most pervasive and abiding
property of malignant cells is their aberrant and unrestrained growth. Normal
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DMOCHOWSKI AND BOWEN
cells grown under laboratory conditions by
any of a number of tissue culture technics have in common the property of "density-dependent growth inhibition". When
these normal cells have grown sufficiently
to make contact, or even reach a certain density of cells without actual contact,
cell movement and division cease and cellular metabolic activities are curtailed to
the point of maintenance of viability without cell growth. T h e complete mechanism
of this contact inhibition of cell growth
is far from clearly understood. Current
evidence supports the idea that cell contact leads to interaction between certain
regulatory macromolecules, probably glycosides, which in turn leads to activation
of membrane-bound enzymes that control the synthesis of small molecular
mediators. T h e change in the concentrations of these mediators results in decrease or cessation of the metabolic activities they regulate, halting cell growth.
Neoplastic cells escape these regulatory
mechanisms and continue to grow free of
the constraints on normal cells by approaching saturation of the growing area.
This continued growth leads to high saturation densities and to irregular multilayered
clusters of cells. Further, cellular adhesion
is reduced in such cells, increasing significantly the tendency of single cells or aggregates to break loose from the larger
cell masses and settle again to resume
growth at a different site. If this phenomenon is transposed from the tissue
culture flask to the tumor-bearing organism, the comparison to metastasis is
readily apparent.
Although the full basis of this tendency
of malignant cells remains to be elucidated, morphologic and cytochemical as
well as biochemical studies of the cell
membranes have provided some insights.
Many electron microscopists have noted
that the cell membrane of tumor cells
A.J.C.P.—Vol.
63
is thicker in appearance than that of
corresponding normal cells.
Shigematsu 24 combined electron microscopy with histochemical technics in an attempt to determine the basis of the differences observed in plasma membranes of
tumor and normal cells using normal cells
and cells derived from tumors induced
by RNA tumor viruses. In these studies,
ruthenium red, a dye that reacts with acid
mucopolysaccharides (AMS) to produce an
electron-dense complex, was used to detect
AMS on normal and tumor cell membranes.
The results of these studies showed
that the surfaces of both normal and virustransformed cells were coated with a layer
of AMS, an observation in agreement
with results of other experimental approaches. The AMS layer of transformed
cells was markedly thicker and denser
than that. of normal cells. T u m o r virus
particles released from the plasma membranes of these cells were also coated with
the AMS material, and budding virus
particles were embedded in the AMS
matrix. A particularly interesting observation in this study was that when ferritinlabeled antibody specific for virus was
applied to these cells, the ferritin granules
indicative of positive reaction were found,
not directly bound to the virus particles,
but in the AMS layer surrounding the
virus particles. These results suggested that
the antigen-antibody reactions may occur
in the AMS matrix. 24
T h e accumulation of AMS and other
similar substances on malignant cells probably plays a role in several aspects of
the modified behavior of these cells, including reduced cellular adhesion, the tendency toward dense, piled-up masses of
growing cells, the ability to grow in semisolid agar, and diminished responses to a
variety of external regulatory stimuli.
In recent studies of cell membrane and-
May
1975
INTRODUCTION: CELL MEMBRANES AND DISEASE
gens in cells producing RNA tumor-inducing viruses, a new common cell-surface
antigen has been described. 32 T h e antigen
is not associated with the budding and
C-type RNA viral envelope and is distinct from any cell-surface antigen associated with murine and feline leukemia
viruses. This cell-surface antigen is present in virus-induced leukemias of mice,
in cells infected with feline leukemia virus,
and in feline spontaneous lymphosarcoma
cells.32 It is not present in normal virusfree mouse, rat, and cat cells. Available
evidence suggests that this common cellsurface antigen is closely related—if not
identical—to a subviral component (P30)
related to gs3, an interspecies cross-reactive determinant—an internal structural
component of C type RNA leukemia
viruses.32 This common cell-surface antigen may be an antigenic expression of
viral genetic information residing in the
leukemic cells.
Considerable progress has been made
in our knowledge of the structure of cell
membranes, their composition, and their
function. Our present symposium will lead
to further progress in this important and
timely area.
It has been the privilege of organizers
of this symposium to obtain the participation of experts on membrane structure and
its relationship to disease at the level of
molecular biology and pathology. Each
participant is a leader in his field exploring the fundamental basis of diseases
in an attempt to provide the practicing
clinician with answers applicable to a
practical understanding of disease, its diagnosis, management, and prevention.
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