CBCL 5: Metastasis Flashcards
What are the steps of metastasis?
i. Transformation of the original cells -> the growth of neoplastic cells is progressive and progressively slow
ii. Angiogenesis occurs, which has a critical role in establishing a vascular network within the surrounding host tissue
iii. Local invasion occurs next - either into the vasculature or the lymphatic system
iv. Detachment and embolization of tumor cell aggregates (within circulation)
v. Circulation of emboli (from step 4) within the vasculation (blood and lymph)
vi. Survival of tumor cells that trafficked through the circulation and arrest in capillary bed
vii. Extravasation of the tumor embolus by mechanisms similar to those involved in the initial tissue invasion
viii. Proliferation of tumor cells within the organ parenchyma -> metastatic focus
ix. Establish vascularization and defenses against host immune responses
Reinitiate these processes for the development of metastases from metastases
What is the process of EMT wrt metastasis?
EMT: rapid and reversible change in cellular phenotypes
a result in the loss of epithelial properties, including cell-cell adhesion and baso-apical polarity, and the gain of mesenchymal properties, such as an increased ability to migrate on invade through extracellular matrix proteins.
associated with loss of expression of proteins involved in the formation of cell-cell junctions, such as E-cadherin, zonula occludens (ZO1) and/or claudin and gain of mesenchymal protein expression
**depression in E-cadherin expression and increase in N-cadherin (found in mesenchymal cells)
