Human and mouse melanoma cells recapitulate an EMT-like program in response to mesenchymal stromal cells secretome.

Human and mouse melanoma cells recapitulate an EMT-like program in response to mesenchymal stromal cells secretome.

Publication date: Mar 31, 2021

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.

Concepts Keywords
Perivascular tumors
B16 metastasis
Profile melanoma
Propensity melanomas
Precursor tumor
Branches of biology
Medical specialties
Oncology
Cancer pathology
Cancer research
Epithelial–mesenchymal transition
Metastasis
Melanoma
C-Met
Mesenchyme

Semantics

Type Source Name
disease MESH melanoma
pathway KEGG Melanoma
disease MESH tumor
disease MESH B16 melanoma
disease MESH metastasis
drug DRUGBANK Methionine

Original Article

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