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. 2014 Oct 11;12:271. doi: 10.1186/s12967-014-0271-5

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© Touboul et al.; licensee BioMed Central Ltd. 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Early steps in peritoneal infiltration. Tumor-associated Mesenchymal Cells (TAMCs) constitute a protective niche for ascitic Ovarian Cancer Cells (OCCs) through their inhibition of anti-cancer T cells. They also participate in angiogenesis at metastatic sites by inducing macrophages production of pro-angiogenic cytokines including IL-6, IL-8 and VEGF. Ascitic OCCs may be the primary source of peritoneal metastases. The initiation of peritoneal invasion relies on the ability of OCCs to attach to and to clear the mesothelial cells that constitute the peritoneum. This mesothelial clearance involves integrin- and talin-dependent activation of myosin and allows OCCs to get access to the basement membrane. Bone marrow-derived Mesenchymal Stem Cells (MSCs) are recruited at metastatic sites and favor the infiltration process with the release of secreted factors such as IL-6 and MMP-2. The metalloprotease MMP-2 is also up regulated in OCCs upon binding to mesothelium and leads to improved attachment of tumor cells by modifying the extracellular matrix.