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Silke Reinartz: Impact of the secretome of inflammatory macrophage subsets on the mesothelial architecture promoting ovarian carcinoma metastasis

AIM: Progression of HGSC is characterized by an early transcoelomic dissemination of tumor cells via the peritoneal fluid (ascites in advanced stages) resulting in extensive peritoneal metastasis which is a hallmark of this tumor entity. Overcoming the protective mesothelial lining is regarded as an essential step preceding tumor cell invasion into the peritoneal tissue. This is supported by the presence of lesions in the mesothelium at metastatic sites. Here we address the mechanisms of secretome-induced mesothelial-to-mesenchymal transition (MMT) in the mesothelium, which facilitates tumor cell invasion and metastasis.

STATE of the ART: Early metastatic spread in the peritoneum is one of the major clinical problems in the treatment of HGSC. In this context, the mesothelium which covers the peritoneal organs takes an important role. Soluble factors in the tumor secretome could trigger a MMT impairing the mesothelial integrity by gap formation and additionally altering the secretory profile of mesothelial cells in a tumor-promoting manner. Whereas previously published data point to the role of tumor cells in the TGFβ-dependent MMT induction in mesothelial cells a direct contribution of immune cells to MMT could not be clearly proven . It is discussed that ascites-derived soluble factors (e.g. TGF-β, IL-1β) as well as EVs may be involved in MMT processes. Among the HGSC TME macrophages comprise a heterogenous, dynamic population displaying distinct phenotypes and functions, however, their role in MMT facilitating metastasis has not been addressed so far.