Heterotypic signaling between dermal fibroblasts and melanoma cells induces phenotypic plasticity and proteome rearrangement in malignant cells

Autor(es)

Pessotti, Dayelle S. ; Andrade-Silva, Debora ; Serrano, Solange M. T. ; Zelanis, Andre

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS; v. 1868, n. 12, p. 9-pg., 2020-12-01.

Resumo

The signaling events triggered by soluble mediators released from both transformed and stromal cells shape the phenotype of tumoral cells and have significant implications in cancer development and progression. In this study we performed an in vitro heterotypic signaling assays by evaluating the proteome diversity of human dermal fibroblasts after stimulation with the conditioned media obtained from malignant melanoma cells. In addition, we also evaluated the changes in the proteome of melanoma cells after stimulation with their own conditioned media as well as with the conditioned medium from melanoma-stimulated fibroblasts. Our results revealed a clear rearrangement in the proteome of stromal and malignant cells upon crosstalk of soluble mediators. The main proteome signature of fibroblasts stimulated with melanoma conditioned medium was related to protein synthesis, which indicates that this process might be an early response of stromal cells. In addition, the conditioned medium derived from 'primed' stromal cells (melanoma-stimulated fibroblasts) was more effective in altering the functional phenotype (cell migration) of malignant cells than the conditioned medium from non-stimulated fibroblasts. Collectively, self- and cross-stimulation may play a key role in shaping the tumor microenvironment and enable tumoral cells to succeed in the process of melanoma progression and metastasis. Although the proteome landscape of cells participating in such a heterotypic signaling represents a snapshot of a highly dynamic state, understanding the diversity of proteins and enriched biological pathways resulting from stimulated cell states may allow for targeting specific cell regulatory motifs involved in melanoma progression and metastasis. (AU)

• Processo FAPESP: 14/06579-3 - Análise sistêmica do processamento N-terminal e diversidade de proteínas no secretoma de células tumorais
• Beneficiário: André Zelanis Palitot Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/07282-8 - Prospecção de marcadores associados a processamento proteolítico em amostras de plasma de pacientes com melanoma
• Beneficiário: André Zelanis Palitot Pereira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/16935-7 - Uma perspectiva sobre as modificações pós-traducionais em toxinas de venenos do gênero Bothrops: identificação proteômica de sítios específicos de N-glicanos e cisteínas.
• Beneficiário: Débora Andrade Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs