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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Cancer Letters; v. 501, p. 114-123, MAR 31 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 19/18702-8 - Geração e avaliação da eficiência antitumoral de linfócitos T CAR com fenótipo T helper 17
• Beneficiário: Heloisa Brand
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 08/08944-0 - Avaliação do papel das células-tronco mesenquimais na progressão tumoral em modelo de metástase experimental de melanoma
• Beneficiário: Lucas Eduardo Botelho de Souza
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs