Cancer Mets Flashcards
what are examples of stromal cells?
fibroblasts, adipocytes, macrophages, endothelial cells, smooth mm cells
what is the tumor “microenvironment”?
describes stromal cells and the substances that they secrete- hormones, cytokines, enzymes
discuss the secretion of PDGF by melanoma cells
PDGF stimulates the release of IGF-2 from fibroblasts, IGF-2 functions as a survival factor and enhances the survival of melanoma cells
what is the “angiogenic switch”?
mechanism that controls the tumor’s ability to make new blood vessels
what occurs during tumor hypoxia?
HIF1a activated
HIF1a stimulates VEGF to proliferate endothelial cells
stromal cells release chemoattracts that stimulate the migration of endothelial cells
what occurs when O2 present?
proline hydroxylase binds to HIF1a, leads to ubiquitination and degradation
describe tumor capillaries
abnormal
larger, loose attachment of pericytes, end blindly/double back, leaky
what are the 6 stages of metastasis?
local invasion intravasation movement through circulation extravasation micro-mets macro-mets
what are the consequences of E-M transformations in tumor cells?
leads to changes in shape, mobility, junction, secretion of growth factors
describe local invasion
secondary to disruption of the normal cell-cell and cell-ECM interactions (through overcoming anokis)
describe intravasation
focal adhesion to endothelial cells occurs through actions of integrins and ECM; WASP contributes to formation of invadopodia; MMP breakdown ECM
what are invadopodia?
formed with actin/WASP
degrade the basement membrane
what are matrix metalloproteinases?
facilitate the breakdown of ECM (basement membrane and outer layer)
what can inhibit MMP?
TGF-b, through the action of PAI-1, can inhibit MMP; thus loss of TGB-b will increase metastasis potential
why does extravasation occur?
cancer cells reach capillary that limits movement and they move out into tissue
what are micro-mets?
cancer cells in distant tissue, but does not meant that clinically significant tumors will result
what is needed for macro-mets?
correct stromal environment
m/c sites of mets for prostate, pancreas, breast and coon CA:
prostate- bone marrow
pancreas- liver
breast- bone marrow
colon- liver
how do tumor cells establish macro-mets?
recruit stromal cells from surrounding tissues (colon CA) or invade existing stroma (breast CA)
describe cancer stem cells
ability to self-renew
slow growing
resistant to XRT and chemo
what are 2 likely sources of cancer stem cells?
1- normal stem cells that undergo malignant transformation
2- cancer cell that undergoes changes to make it more like a stem cell
