TUMOUR MICROENVIRONMENT

Question 1

Introduction about tumor microenvironment

Answer 1

Support tumor growth and survival of tumor cells
Components
Induced by the tumor itself
Focus on MSCs and their functional properties

Question 2

MSCs role in tumor growth

Answer 2

Anti-apoptosis vs pro-apoptosis: anti-apoptosis via induction of STAT3, MAPK and Bcl2
Pro-proliferative vs anti-proliferative: pro-proliferative vs ovarian carcinoma (induction via IL-6) and anti-proliferative vs breast cancer cells via down regulation of survivin, beta-catenin and c-MYC
Pro-angiogenesis
Support of tumor growth rather than inhibition > cannot use MSCs as they are
Differentiation into TAFs
Immunomodulatory functions only in the presence of an inflammatory environment (NK cells)
Recruitment to the tumor site (inflamed site) > exploit them as carriers or vectors of other
anti-cancer molecules

Question 3

TAFs

Answer 3

Characteristics
Constitutive activation of TGF-beta signaling due to loss of caveolin-1 (ex. negative prognostic marker in breast cancer)

Question 4

MSCs in metastasis

Answer 4

Recruitment
Induction of metastatization ex. mammary carcinoma cells infused subcutaneously and lung metastasis
Formation of a pro-tumorigenic environment in the bone marrow to favour metastasis formation ex. neuroblastoma metastasis in BM