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24 Cards in this Set

  • Front
  • Back
How can tumors cause sustained angiogenesis?
By stimulating host blood vessel growth
What factors do tumors secrete to stimulate angiogenesis?
Once newly formed vessels are made, how does angiogenesis CONTINUE?
The endothelial cells also secrete growth factors
What are 4 features of tumor vessels that make them different from normal vessels?
-Produced continuously
-Tortuous and irregular
-Allow for metastasis
What are 3 angiogenesis inhibitors that can be given as treatment?
-Anti-VEGF and VEGF-R2
What is the primary cause of cancer-related morbidity and mortality?
Invasion and metastasis
2 things need to happen for a metastasis to occur:
1. Invasion of ECM
2. Vascular dissemination
So what are the 2 properties that predispose a cancer to metastasis?
-Tumor cell properties
-Stromal properties
What are 4 theories of metastatic mechanisms?
1. Tumor develops variants capable of metastasizing
2. Tumor starts out with a metastatic gene signature
3. Tumor starts out with signature ability, AND develops variants
4. Tumor relies on STROMAL ecm to allow it to metastesize
What happens in general when tumors invade surrounding tissue?
-Cells loosen from each other
-Tumor degrades and remodels the basement membrane
-Creates passageway for migration
What gets degraded in the course of basement membrane degradation?
Type IV collagen
What factors get released during invasion?
-Angiogenic factors
-Anti-angiogenic factors
What are the anti-angiogenic factors again?
How do tumor cells create a passageway for migration?
1. The tumor cells themselves release proteases
2. Tumor induces stromal fibroblasts and macrophages to release proteases
What keeps tumor cells attached to the basement membrane?
Laminin and Fibronectin receptors attached to their appropriate ligands in the BM.
What happens to the laminin receptors on tumor cells as they invade tissue?
They are expressed all around the cell instead of just on the basolateral side
What is increased density of laminin receptors on tumor cells associated with?
More rapid invasion and metastasis.
What are the 5 main steps in the Metastatic Cascade?
1. Breech the BM under 1' tumor
2. Traverse interstitium
3. Get into bloodstream
4. Vascular dissemination
5. Home to new tissue site
What happens to tumor cells when they get into the bloodstream?
They clump
What are 2 things that make tumor cells clump in the bloodstream?
1. Homotypic adhesions between tumor cells
2. Heterotypic adhesions between tumor cells and platelets
Why would tumor cells LIKE being clumped via platelets?
It protects them from immune detection and enhances their ability to implant in the BM.
What do tumors typically consider "unfavorable soil" for tumor seedlings?
Skeletal muscle
What tissue has been shown to drive changes that promote cancer?
Stromal tissue - the extracellular matrix.
Why is it useful to know that the stroma influences carcinogenesis?
It provides another potential therapeutic target.