Neoplasia: Invasion and metastasis (lab) Flashcards
Define metastasis
the transfer of malignant cells from the primary site to a non-connected (secondary) site
What are the three mechanisms of metastasis, and where do they occur?
lymphatogenous: lymph
hematogenous: blood
cavitary: body cavities
T/F: metastases will not penetrate most organs
False
They recognize no anatomical boundaries
What are the steps of the metastasis cascade? (4)
- Invasion through basement membrane & ECM
- Intravasation
- Extravasation
- Colonization
What’s the difference between extravasation and intravasation?
Intravasation: getting into blood OR lymph
extravasation: getting out of vessel at site
What theories are there to explain the bias of metastasis of certain types of cancer towards certain organs?
- Clonal evolution model
- Early on the tumor develops a metastasis “signature”
- A third hypothesis suggests that background genetic variation, and the resulting variation in gene expression in the human population contributes to the generation of metastases.
- tumor microenvironment and influences like chronic inflammation
Explain the clonal evolution model
As tumor accumulates mutations, a subset of the cells (metastatic subclones) develop the right combination of gene products to complete all the steps involved in metastasis.
What are the four steps of invasion?
Step 1: Dissociation of cells from one another
Step 2: Local degradation of basement membranes and interstitial connective tissue
Step 3: changes in attachment of tumor cells to ECM proteins
Step 4: Locomotion
Why do the epithelial cells dissociate from one another in tumors?
In epithelial tumors e-cadherin is downregulated, reducing the ability of cells to adhere to each other
What happens when ZEB1 is expressed?
E-cadherin is repressed
^also repressed by loss of heterozygosity, mutations
What is the Epithelial to Mesenchymal Transition (EMT)?
When cells lose epithelial characteristics and become more tumor-like (less differentiated, able to travel through vessels, etc.)
Decrease E-cadherin
Increase mesenchymal proteins
What is the “seed and soil” theory?
1889- Organ-specific patterns were explained by the needs of the cancer cell (seed) for a specific environment (the soil) to initiate and maintain growth
Organ tropism = specific pattern for organ metastasis
Explain dormancy
Prolonged survival of micrometastases without progression
-happens with melanoma, breast cancer, prostate cancer
What motivates cancer cells to metastasize?
In the primary tumor it becomes advantageous to move away from the primary tumor when conditions get crowded & harsh (hypoxia caused by limited blood supply and lack of nutrients).
Explain the process of locomotion
In the last step of invasion
=Propelling tumor cells through the degraded basement membranes
Cells must attach to matrix at leading edge, detach from the matrix at the trailing edge, and contract the actin cytoskeleton to ratchet forward
