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Metastasis inhibition in breast cancer by targeting cancer cell extravasation

Authors Cominetti MR, Altei WF, Selistre-de-Araujo HS

Received 5 September 2018

Accepted for publication 4 March 2019

Published 18 April 2019 Volume 2019:11 Pages 165—178

DOI https://doi.org/10.2147/BCTT.S166725

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Professor Pranela Rameshwar


Márcia R Cominetti,1 Wanessa F Altei,2 Heloisa Sobreiro Selistre-de-Araujo2

1Department of Gerontology, Federal University of São Carlos, São Carlos, SP, Brazil; 2Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, Brazil

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


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