2: Melanoma, Metastasis and tumor Micro-environment

Question 1

what is hypoxia?

Answer 1

low levels of blood/oxygen

Question 2

order of Metastasis?

Answer 2

primary tumor formation → . local invasion → intravasatien (blood vessels) → survival in blood circulation → extravasation (secondary tissue) → micro nietastasis formation → Metastatic colonization → detectable macroscopic Metastases

Question 3

Where is ALCAM expressed?

Answer 3

in the invasive front off the vertical growth fase of a tumor

Question 4

features ALCAM?

Answer 4

• Member of immunoglobulin super family
• 2 V- type IG domains, 3 C-type domains
• heterophilic (CDC) and homophilic (ALCAM-ALCAM) interaction

Question 5

BLM -dN mutant difference ?

Answer 5

only D3 -D5 domains

Question 6

BLM -S difference?

Answer 6

only D1 domain Which is soluble

Question 7

how is the normal Melanocyte- keratinacyte interaction?

Answer 7

keratinocyt is in control of Melanocyte
- adherens Junction connections by E-cadherin
- Gap junctions
- Melanocyt bound to basement membrane by molecules

Question 8

altered Melanocyt - keratinocyte interaction?

Answer 8

• Detach from keratinocytes and basement Membrane
• New connections with fribroblasts and other melanoma cells

Question 9

how do Melanocyts escape from the control by keratinocytes?

Answer 9

• down - regulation receptors important for communication with Keratinocytes
• up- regulation receptors and signaling molecules important for Melanoma- Melanoma and Melanoma- fibroblast interactions
• loss of anchorage to basement membrane because of an altered expression of the Extracellular-matrix binding integrin family

Question 10

of which 4 catagories consists the Tumor microenvironment?

Answer 10

• Cancer cells
• Non- cancer cells
• Secreated soluble factors
• non-cellular solid material such as ECM

Question 11

what type of Cancer cells are there?

Answer 11

• normal cancer cells → build op the tumor
• invading / migrating cancer cells → invasion and metastasis
• Cancer stem cells → build and maintain the tumor (dormant cells)

Question 12

what non-cancer cells can you find in the TME?

Answer 12

• Endothelial cells → angiogenesis
• Immune cells
• stem cells
• cancer - associated fibreblasts (CAF) → most abundant, produce collageen - remodeling, contribute to growth and invasion

Question 13

types of Secreated soluble factors in TME?

Answer 13

proteases → matrix remodeling, angiogenesis , Release growth factors from the matrix, remodel cell-cell interactions and cell-matrix, Migration and release cells from tumor, intravasatien, activate other protease s or chemolines, basement degradation
- MMP-s important protease → degrades/ remodels collagen in ECM

Question 14

function Non - cellular solid material such as ECM?

Answer 14

• complex network of fiber -forming proteins interwoven in hydrated polysacharide gel
• helps hold cells and tissue together
• provides Meshwork for cells to migrate on and interact with one and another
• influences cell development, migration,proliferation, shape and Metabolic function

Question 15

What is the seed and soil theory?

Answer 15

There seems to be a favourite organ for most cancer Where metastasis occurs (not random)
The cell (seed) reeds a certain type of Micro-environment (soil)