Human and mouse melanoma cells recapitulate an EMT-like program in response to mesenchymal stromal cells secretome. (31st March 2021)

• Record Type: Journal Article
• Authors: de Souza, Lucas Eduardo Botelho; Ferreira, Fernanda Ursoli; Thome, Carolina Hassibe; Brand, Heloísa; Orellana, Maristela Delgado; Faça, Vitor Marcel; Fontes, Aparecida Maria; Covas, Dimas Tadeu
• Is Part Of: Cancer letters. Volume 501(2021)
• Page Start: 114
• Page End: 123
• Publication Date: 2021-03-31
• Subjects: Mesenchymal stromal cells -- Melanoma -- Metastasis -- Epithelial-to-mesenchymal transition -- Hepatocyte growth factor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2020.12.030
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: The mechanisms underlying the propensity of melanomas to metastasize are not completely understood. We hypothesized that melanoma cells are capable of promptly activating an epithelial-to-mesenchymal transition (EMT)-like profile in response to stroma-derived factors. Thus, we investigated the role of mesenchymal stromal cells (MSCs), a cell population considered as a precursor of tumor stroma, on the activation of an EMT-like profile and acquisition of metastatic traits in melanoma cells. After subcutaneous co-injection with mouse B16 melanoma cells, MSCs occupied perivascular sites within tumors and enhanced B16 metastasis to the lungs. In vitro, MSCs' secretome activated an EMT-like profile in B16 cells, reducing their avidity to fibronectin, and increasing their motility and invasiveness. These effects were abrogated upon blocking of MET phosphorylation in B16 cells using small molecule inhibitors. MSCs also activated an EMT-like profile in human melanoma cells from different stages of progression. Activation of EMT in human cells was associated with increased levels of p-STAT1 and p-STAT3. In conclusion, both mouse and human melanoma cells are equipped to activate an EMT-like program and acquire metastatic traits through the activation of distinct pathways by MSCs' secretome. Highlights: Mouse bone marrow MSCs (mMSCs) occupy the perivascular space in melanoma tumors and enhance metastasis. MMSCs induce EMT and enhance metastatic traits in B16 melanoma cells via HGF/MET signaling. Human bone marrow MSCs (hMSCs) also induce EMT in melanoma cells from different stages of progression. EMT induced by hMSCs is associated with higher levels of p-STAT1 and p-STAT3.