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

Author(s)

Botelho de Souza, Lucas Eduardo ^{[1, 2]} ; Ferreira, Fernanda Ursoli ^{[1, 2]} ; Thome, Carolina Hassibe ^{[2, 3]} ; Brand, Heloisa ^{[1, 2]} ; Orellana, Maristela Delgado ^{[1, 2]} ; Faca, Vitor Marcel ^{[2, 3]} ; Fontes, Aparecida Maria ^[4] ; Covas, Dimas Tadeu ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Clin Med, 3900 Bandeirantes Ave, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Hemotherapy Ctr Ribeirao Preto, Ctr Cell Based Therapy, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, 3900 Bandeirantes Ave, BR-14048900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, 3900 Bandeirantes Ave, BR-14048900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Cancer Letters; v. 501, p. 114-123, MAR 31 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 19/18702-8 - Generation and evaluation of antitumor efficiency of CAR-T cells harboring a T helper 17 phenotype
• Grantee: Heloisa Brand
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 08/08944-0 - The role of mesenchymal stem cells in cancer progression in a mouse melanoma model
• Grantee: Lucas Eduardo Botelho de Souza
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC