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. 2019 Apr 18:11:165-178.
doi: 10.2147/BCTT.S166725. eCollection 2019.

Metastasis inhibition in breast cancer by targeting cancer cell extravasation

Márcia R Cominetti  1 , Wanessa F Altei  2 , Heloisa Sobreiro Selistre-de-Araujo  2
Affiliations

Metastasis inhibition in breast cancer by targeting cancer cell extravasation

Márcia R Cominetti et al. Breast Cancer (Dove Med Press). .

Abstract

The spread of cells from primary tumors toward distant tissues and organs, also known as metastasis, is responsible for most cancer-associated deaths. The metastasis cascade comprises a series of events, characterized by the displacement of tumor cells (TCs) from the primary tumor to distant organs by traveling through the bloodstream, and their subsequent colonization. The first step in metastasis involves loss of cell-cell and cell-matrix adhesions, increased invasiveness and migratory abilities, leading to intravasation of TCs into the blood or lymphatic vessels. Stationary TCs must undergo the process of epithelial-mesenchymal transition in order to achieve this migratory and invasive phenotype. Circulating tumor cells that have survived in the circulation and left the blood or lymphatic vessels will reach distant sites where they may stay dormant for many years or grow to form secondary tumors. To do this, cells need to go through the mesenchymal-epithelial transition to revert the phenotype in order to regain epithelial cell-to-cell junctions, grow and become a clinically relevant and detectable tumor mass. This work will review the main steps of the metastatic cascade and describe some strategies to inhibit metastasis by reducing cancer cell extravasation presenting recent studies in the context of breast cancer.

Keywords: breast cancer; circulating tumor cells; extravasation; metastasis.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic representation of the metastatic cascade steps in breast tumors. Cells in the primary tumor undergo epithelial-mesenchymal transition (EMT), acquiring migratory and invasive properties. After leaving the primary tumor, cells enter into circulatory or lymphatic vessels until extravasation to a distant metastatic secondary site represented in the scheme by a bone. Once established at the secondary site, cells suffer an inverse EMT process called mesenchymal-epithelial transition (MET). The drawing has no anatomical proportions. Abbreviation: CTC, circulating tumor cells.
Figure 2
Figure 2
Metastasis cascade and the currently explored targets and their inhibitors. Data from Wojtukiewicz et al, Marcucci et al, Raab-Westphal et al, Rosel et al, and Sini et al. Bevacizumab and antiplatelets compounds are commercially available, while drugs targeting EMT and migration are in clinical trials (clinicaltrials.gov). Anti-invasion drugs, known as migrastatics, are under experimental investigations. Abbreviations: VEGF, vascular endothelial growth factor, EMT, epithelial-mesenchymal transition, MET, mesenchymal-epithelial transition.
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