melanoma + tumor microenvironment

Question 1

melanoma

Answer 1

skin cancer, comes from melanocytes, usually due to overexposure to UV light causing mutation to melanocytes

Question 2

explain the development of melanoma from benign nevus to metastasis

Answer 2

1. benign nevus
2. dysplastic nevus: atypical mole with irregular features. These moles have a higher risk of becoming cancerous. here BRAF mutation is observed
3. radial growth phase: the melanoma cells spread horizontally within the top layer of the skin (epidermis)
4. vertical growth phase: The melanoma cells begin to grow downward into the deeper layers of the skin (dermis).
5. metastasis: melanoma cells break away from the primary tumor and travel through the bloodstream or lymphatic system to other organs and tissues.

Question 3

angiogenesis

Answer 3

the formation of new blood vessels (neovasculature) from existing ones
process
1. tumor microenv. in hypoxic condition secretes HiF (hypoxia inducing factor)
2. HiF will induce VEGF expression which will be received by VEGFR in endothelial cells
3. endothelial cells will form the blood vessels

Question 4

seed and soil theory

Answer 4

This theory suggests that the spread of cancer (metastasis) is not random. Instead, it depends on the interaction between cancer cells (the “seeds”) and the specific organ environments (the “soil”) they land in
Seeds: These are the cancer cells that break away from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body12.
Soil: This refers to the specific organ environments that the cancer cells land in. For metastasis to occur, the environment must be conducive to the growth and survival of the cancer cells

Question 5

explain tumor microenvironment

Answer 5

1. cancerous cells:
   There are normal cancer cells, that build up the tumour. Invading/migrating cancer cells for invasion and metastasis.
   Cancer stem cells that build up and maintain the tumour
2. non-cancerous cells:
   Endothelial cells (for angiogenesis), cancer-associated fibroblasts (produce ECM), immune cells, and stem cells
3. soluble secreted factors: cytokines, chemokines, growth factors, and proteases
4. non-cellular materials: ECM

Question 6

old and new view of metastasis

Answer 6

● Old view: primary tumor, cells detach,
and metastasis
● New view: Primary tumor, factors that are secreted mobilize the bone marrow-derived cells as they go to the pre-metastatic niche, and will attract cells from the primary tumor to settle and grow there. These cells then can detach again and travel back to the primary tumor to also grow over there.