Organo Tropism and Tumor Metastasis

Introduction

Organo Tropism (Organ Honing): Tendency of cancer cells to metastasize to specific organs.
Example: Breast cancer cells often spread to the lung, liver, and brain.
Key Question: Why do certain tumors spread to particular organs?

Seed and Soil Hypothesis: Suggests tumors grow well in secondary organs similar to their origin.
- Hypothesis includes the idea that tumors thrive in tissues similar to their germline tissue.
- Largely conjecture; not fully understood.

Circulatory Arrest
- Mechanism: Cancer cells arrest at the first capillary bed they encounter.
- Example: In mice, injecting cells into the left ventricle leads to brain metastasis.
- Injection Sites:
  - Tail vein → lung metastasis.
  - Left ventricle → brain metastasis.
- Cell Characteristics: Tumor cells are larger and get stuck in capillaries.
Gene Expression and Transcription Factors
- Key Gene: Twist, an embryonic transcription factor.
- Function: Enables cell motility and inappropriate expression aids metastasis.
- Process: Tumor cells use twist to express metalloproteases, which dissolve adhesion molecules in blood vessel walls.
Endothelial Integrity and Tissue Characteristics
- Blood Vessel Integrity: Affects how easily cancer cells can exit.
- Bone Metastasis:
  - Blood vessels in bone have fenestrations, allowing easy passage of cells.
  - Fenestrations are necessary for hematopoietic stem cells.
- Brain Metastasis:
  - Brain protected by blood-brain barrier (BBB), making metastasis difficult.
  - Barrier Components:
    - Tight endothelial cells.
    - Pericytes provide a second protective layer.
    - Astrocytes and microglia form the brain's immune defense.

Three Factors: Circulatory path, gene expression, and vessel integrity dictate where cancer cells metastasize.
Barrier Example: Brain is less likely to be a metastatic site due to the BBB and immune defenses.