Lecture 11: Invasion and metastasis

Question 1

Radially vs vertically growing melanomas, which metastasize ?

Answer 1

Radially rarely metastasize: only few, sparse tumor cells in dermis
Vertical nearly always metastasizes: tumor mass in dermis and epidermis

Question 2

Why do the lungs and liver get higher dose of tumor cells

Answer 2

Their blood capillaries are the first to trap blood-borne disseminating cells

Question 3

Two ways cancer cells can disseminate

Answer 3

Hematogenous : via the blood vessels
Lymphatic : spreading to the draining lymph node

Question 4

How do cancer cells spread beyond the lymph nodes ?

Answer 4

Lymphatics that drain into the subclavian vein near the heart

Question 5

By what is metastasis driven ?

Answer 5

Epigenetic and/or reversible transcriptional alterations (no additional mutations)

Question 6

6 steps to spawn distant metastases

Answer 6

• Localized invasion
• Intravasation
• Transport through circulation and arrest in microvessels of various organs
• Extravasation
• Formation of a micrometastasis
• Colonization - formation of a macrometastasis

Question 7

What is the rate limiting step of the invasion-metastasis cascade ?

Answer 7

Colonization

Question 8

Do most cells make it past extravasation ?

Answer 8

No, most disseminating cells die before, few form ‘dormant’ micrometastases of quiescent cells

Question 9

What mediates cell adhesion to ECM ? (diversity)

Answer 9

Integrins:
- ≥24 distinct heterodimers, great versatility

Question 10

Functional roles of integrin adhesion to ECM

Answer 10

• Organize intracellular acin cytoskeleton
• cell-substrate adhesion -> cell survival signals
• Focal adhesion kinas (FAK): stimulation of cell proliferation

Question 11

What does recruitment of FAK activate ?

Answer 11

Ras/PI3K survival signaling mediated by Akt