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How and when do tumor cells metastasize?
M M Mareel1, F M Van Roy, M E Bracke
1Department of Radiotherapy and Nuclear Medicine, University Hospital, Gent, Belgium.
Abstract:
Tumor cells metastasize when they have successfully passed a number of invasion steps. We hypothesize that each step is a microecosystem, the basic elements of which are neoplastic cells, host cells, and extracellular matrix (ECM). We review here molecular pathways with a regulatory function in these microecosystems: homotypic cell-cell adhesion molecules counteracting invasion; complexes of lytic (pro-)enzymes, their receptors and inhibitors regulating focalized breakdown of the ECM; matrix components, their cellular receptors and motility factors governing cell migration; heterotypic cell-cell adhesion molecules initiating extravasation, encompassing in the vasculature the sequence: cell arrest, ECM lysis, cell migration; factors allowing survival and growth at ectopic sites. We conclude that delicate molecular balances within microecosystems are responsible for the temporary and repeated invasion events leading to metastasis.
Insights
Metastasis involves tumor cells navigating sequential microecosystems. Molecular balances regulating cell adhesion, extracellular matrix (ECM) breakdown, and migration are key to these invasion steps.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Tumor cell metastasis is a complex, multi-step process.
- Each step is hypothesized to represent a distinct microecosystem.
- These microecosystems involve neoplastic cells, host cells, and the extracellular matrix (ECM).
Purpose of the Study:
- To review molecular pathways regulating microecosystems in tumor metastasis.
- To elucidate the role of molecular balances in invasion and metastasis.
Main Methods:
- Literature review of molecular pathways involved in metastasis.
- Analysis of molecular mechanisms governing cell-cell adhesion, ECM degradation, and cell migration.
- Examination of factors influencing survival and growth at ectopic sites.
Main Results:
- Homotypic cell-cell adhesion molecules inhibit invasion.
- Lytic enzyme complexes and their regulators control ECM breakdown.
- ECM components, receptors, and motility factors drive cell migration.
- Heterotypic cell-cell adhesion molecules mediate extravasation.
- Specific factors facilitate survival and growth in ectopic sites.
Conclusions:
- Metastasis is driven by sequential invasion steps within microecosystems.
- Precise molecular balances within these microecosystems control invasion events.
- Understanding these balances is crucial for targeting metastasis.