Metastasis inhibition in breast cancer by targeting cancer cell extravasation

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
• metastasis
• extravasation
• circulating tumor cells

Acknowledgments

The authors would like to thank Lia Mara Grosso Neves for preparing Figure 1. This work was supported by FAPESP (São Paulo Research Foundation, grants #2013/00798-2, 2015/24940-8, and 2014/1 8747-8), CAPES (Coordination for the Improvement of Higher Education Personnel), and CNPq (National Council for Scientific Research).

Author contributions

All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work. All authors contributed equally to the writing of the manuscript. WFA prepared Figure 2.

Disclosure

The authors report no conflicts of interest in this work.