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Cancer Summit 2007
Using Time-lapse Microscopy to Learn
How Tumor Cells Migrate & Invade
Covering the distance between discovery and treatment
is a team effort
No one research group can
do it alone
The significance of new
discoveries is not always
immediately obvious
Initial
discovery
Recognition
of relevance
Early
Animal Clinical
experiments studies & Trials
drug
development
New
Treatment
Discoveries relevant to cancer treatment can come from
unexpected places
1950s
Discovery of
Nerve Growth Factor
Rita Levi-Montalcini
1960s
Characterization of
Epidermal Growth
Factor (EGF)
Stanley Cohen
1980s
Identification of
EGF Receptor
1998
Herceptin approved
for treatment of
metastatic
breast cancer
Covering the distance between discovery and
treatment is a team effort
No one research group can
do it alone
The significance of new
discoveries is not always
immediately obvious
“Basic” biomedical research
Initial
discovery
Recognition
of relevance
Early
Animal Clinical
experiments studies & Trials
drug
development
New
Treatment
Metastasis is responsible for most cancer-related
deaths but remains poorly understood
Metastasis in
non-Hodgkins
lymphoma
Figure 14.1 from “The Biology of
Cancer,” Robert A. Weinberg,
2007, Garland Science
Tissues are composed of orderly arrays of many
individual cells
Cells use proteins to accomplish necessary functions
Information encoded by
genes is used to produce
individual proteins
Proteins fold into many different
shapes to fulfill different functions
Epithelial cells use proteins to interact with each and
with the “extracellular matrix”
cell adhesion molecules
“matrix” receptors
Cancer progression involves changes in cell-cell and
cell-matrix interactions
Cell-cell interactions may be disrupted
Cell-matrix interactions may be used
for invasion and migration
Tumor cells can be propagated & studied in the lab
Incubator
Flasks & growth medium
Biosafety cabinet
Cell culture microscope
Time-lapse video-microscopy can be used to study
tumor cell behavior
Different tumor cell responses to different matrix proteins
QuickTime™ and a
None decompressor
are needed to see this picture.
protein A
protein B
protein C
mixture of different matrix proteins
Tumor cells use different matrix receptors to respond to
different matrix proteins
Receptor A
matrix protein A
(slow migration)
matrix protein B
(medium migration)
“Receptor C”, which
allows the most rapid
migration, has extra
accessory proteins
Receptor B
Receptor C
matrix protein C
(fast migration)
Removing accessory proteins from the migrationpromoting matrix receptor attenuates tumor cell motility
QuickTime™ and a
Sorenson Video 3 decompressor
are needed to see this picture.
Migrating tumor cells must “let go” at the rear in order
to keep moving forward
Loss of “Receptor C” accessory proteins may impair
the ability of tumor cells to “let go” during migration
QuickTime™ and a
Sorenson Video 3 decompressor
are needed to see this picture.
Tumor cells engineered to glow like fireflies can be used
to follow disease in mouse models of cancer
Acknowledgments
Lab Members
Collaborators
Research Associates
Afshin Varzavand
Nicole Winterwood
Jess Johnson
Michael Henry, University of Iowa
Postdoctoral Fellow
Mary Herndon
Leonie Ashman
University of Newcastle, Australia
Sponsors
American Cancer Society
Graduate Student
Shannin Zevian
Carver Foundation
Department of Defense
U.I. Biosciences Funding Program