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Tumors arise from normal tissues
Tumors are created by cells that have lost the ability to
assemble and create tissues of normal form and function
Depending on the degree of aggressive growth – tumors
can be classified as benign (grow locally without invading
adjacent tissues) or malignant (invade nearby tissues and
spawn metastases)
Most tumors are derived from a single abnormal cell
Cancer cells contain somatic mutations
A single mutation is not enough to cause cancer
Cancers develop gradually from increasingly aberrant cells
Tumor progression involves successive rounds of random inherited change
followed by natural selection
Cancer cells undergo epigenetic and genetic changes
A small population of cancer stem cells maintains many tumors
Metastasis is the cause of 90% of deaths from solid tumors
Primary tumors and their metastatic tropisms
Characteristic features of metastasis – steps in a cascade
- loss of cellular adhesion
- increased motility and invasiveness
- entry and survival in the circulation
- exit into new tissue
- eventual colonization of a distant site
Steps in the process of metastasis
Travel of cancer cells from a primary tumor site to a site
of potential metastasis depends on a series of complex
biological steps
The invasion-metastasis cascade
Mutations that lead to metastasis are still a mystery
Barriers to metastasis
Colonization represents the most complex and challenging step
of the invasion-metastasis cascade
Steps leading to extravasation
The epithelial-mesenchymal transition (EMT) and associated loss
of E-cadherin expression enable carcinoma cells to become
The tumor microenvironment influences cancer development
The epithelial-mesenchymal transition (EMT) is often induced by
stromal cells
COX2 – prostaglandin-synthesizing enzyme (cyclooxgenase-2) – promotes extravasation in the
lungs; prostaglandin production during inflammation increases blood-brain barrier permeability
HBEGF – Heparin-binding EGF – EGFR ligand – induces cancer cell motility and invasiveness
ST6GALNAC5 – a 2,6-sialyltransferase – catalyses the addition of sialic acid to gangliosides and
glycoproteins; makes cell more adhesive and mediates infiltration into the brain