Biology Of Metastasis

Question 1

What is the rate limiting step of metastasis?

Answer 1

Survival of cancer cells at secondary sites

Question 2

What makes the cells more plastic?

Answer 2

Growth factors, loss of cell to cell adhesion, and changes to cell matrix variation

Question 3

What molecular factors stop EMT?

Answer 3

Tgf-b, tnf-a

Question 4

What are some transcription factors that orchestrate EMT?

Answer 4

Snail, slug

Question 5

Is metastasis by single cell seeding or collective seeding? What evidence points to that?

Answer 5

Collective seeding

Tumour sphere inverted polarity

Question 6

What’s the role of stem cells in EMT?

Answer 6

It gives the heterogeneity of the originating primary tumour.

Question 7

What are the theories to explain the patterns seen in metastasis?

Answer 7

Seed and soil- explain that cells recognize specific receptors(Chemokines) on the tissue they can adhere to and extravasate into, this changes with the type of tissue. Explains the unusual metastasis
Mechanical hypothesis- metastasis depends on blood supply and anatomy, these cells will lodge and invade the first capillary bed they encounter. Doesn’t explain unusual patterns seen.
Clonal selection- different clones within the same tumour has a rare selective advantage that allows it to metastasize where other clones won’t survive. They don’t all have the same metastatic ability
Metastasis signature hypothesis- most sunsets of tumour have metastatic genes that allow to them to metastasize if conditions are favourable

Question 8

How does breast cancer metastasis to the bone work? What hypothesis does this support?

Answer 8

A small subset in the breast tumour accumulate genes that allow it to metastasize to the bone, there they destruct the bone reaping growth factors that increases expression of metastasis genes. Clonal selection

Question 9

What are some examples of metastasis signature genes? Metastasis oncogenes?
Metastasis suppressor genes?
Implications for therapy?

Answer 9

Cxcr4
Mmp1
C-erb, osteopontin
Kiss-1 rkip 
Can target against them or restore their function depending on which is mutated

Question 10

More evidence supports the clonal selection hypothesis

Answer 10

True

Question 11

What upregulates cxcr4?

Answer 11

Erbb2

Question 12

Where can unknown primary tumours come from?

Answer 12

Cancer stem cells

Question 13

Where do most cancer cells metastasize when the intravasate blood or lymph? why?

Answer 13

Lymph

Question 14

How do TAM induce metastasis?

Answer 14

The tumours have soluble Csf that recruits macrophages and they become trophies to them supllying them with proteases to break their basement membranes and remodel stromal matrix, goes to hypoxic area and produces vegf induce angiogenesis and growth factors and chemokines a

Question 15

How do cancer associated fibroblasts work?

Answer 15

Enhance tumour phenotypes by immunosuppression

Question 16

What are the main challenges metastatic cells have to overcome?

Answer 16

1. Immune system
2. lymphaptic and circulatory system
3. anatomy

Question 17

Is metastasis effiecient? Why if it’s preprogrammed?

Answer 17

No need to overcome many hurdles to migrate, invade and colonize another tissue
Because genetic make up may influence the efficiency

Question 18

Metastatic spread can take place through mutiple route and in different directions

Answer 18

True

Question 19

Decrease in proliferative rate and increase in cell death increases tumour growth

Answer 19

True. By increasing metastasis

Question 20

What are two theories in how metastasis takes place in a new site?

Answer 20

Directly by primary tumour send cells to the secondary site
Exome printing send tiny packets of rna and protein to the new site preparing for invasion and to the bone marrow cells to go to future site, this is a premetastaic niche

Question 21

What is in the premetastaic niche?

Answer 21

Different immune cells such as macrophages, treg, vegf, stromal cell, it’s hypoxic creates a perfect environment for the cancer cells to thrive