Module 1: Cellular and Developmental Neurobiology

Question 1

Lecture 8 - What is the metastatic cascade?

Answer 1

0) Being induced by a distant tumor and mediated by bone marrow-derived cells, a “premetastatic niche” forms before metastasis becomes evident.
1) Cells in the primary tumor undergo Epithelial–Mesenchymal Transition (EMT) and acquire invasive properties.
2) Degradation of basement membranes and remodeling of the ExtraCellular Matrix (ECM) by proteinases facilitate tumor cell invasion.
3) Tumor cells invade surrounding tissue as single cells (3a) or collectively (3b).
4) Intravasation of tumor cells into newly formed vessels within or nearby the tumor.
5) Tumor cells are transported through the vasculature and arrest in a capillary bed where they extravasate (6).
7) Extravasated tumor cells can stay dormant for years.
8) Eventually, some disseminated cells grow out to a secondary tumor / macrometastasis, requiring ongoing ECM remodeling and angiogenesis
(9) . Cells outside their normal microenvironment undergo anoikis (“detachment-induced apoptosis”). Anoikis could hamper metastasis at several steps of the cascade, as indicated in the scheme. Not all steps of the metastatic cascade necessarily occur in a linear way. For example, premalignant tumors can already be vascularized while the timing of induction of the premetastatic niche remains elusive.