Biology of Metastasis

Question 1

Know the major determinants of tumor metastatic potential

Answer 1

1) Histotype
(highly metastatic) 
- hemangiosarcoma 
- OSA
- malignant melanoma 
- ASAGAC

2) histologic grade
- high grades are more likely to metastasis

3) Size
- the bigger the tumor, the more likely it is to metastasis

Question 2

Understand the hurdles that tumor cells must overcome in order to successfully form a metastatic site

Answer 2

1) Motility and Invasion
- detach from each other
- move to a new location

2) Embolism and Circulation
- survive in circulation
- avoid immune system

3) Capillary Arrest/Adhesion
- survive after capillary arrest (shear stress, etc)
- bind to specific receptors on the target organ endothelium (sometimes)

4) Extravasation

5) Survival and proliferation in new microenvironment
- Rate Limiting Step!

Question 3

Understand how and why a tumor develops its blood supply

Mechanisms of Angiogenesis

Answer 3

• limit of diffusion for O2 in tissues 200um –> beyond this, cells become hypoxic –> tumors need their own blood supply

MOA - Angiogenesis:

1) ingrowth of endothelial cells from existing vessels
2) outgrowth and recruitment of circulating endothelial precursors from blood**
3) vasculogenic mimicry, mosaicism

Question 4

Give an example of a treatment that might target tumor blood vessels

Answer 4

Block angiogenic growth factors

• Abs
• small molecules

“Avastin” - bevacizumab

Question 5

How often does metastasis occur?

Answer 5

1/3 of cancers have metastasis at time of dx

1/3 have microscopic metastasis at presentation & will develop detectable mets in the future

1/3 are cured with local therapy alone –> mets never occur

Question 6

How does cancer spread to different parts of the body? Give examples of each

Answer 6

1) Direct Extension
- hemangiosarcoma (rupture –> seeding into peritoneal cavity)
- ovary, lung, CNS (human)

2) Lymphatics
- carcinomas, Round Cell tumors

3) Hematogenous
- sarcomas, carcinomas

Question 7

Two theories on cancer spread

Answer 7

1) Mechanistic Theory
- the first site to which a cancer metastasizes is the closest one in which there are small blood vessels

2) Seed and Soil Theory
- cells are dispersed randomly but only grow in organs which provide the correct factors necessary for growth of that particular tumor (fertile soil)

**Probably a combo of both