Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer

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Autor(es): dc.contributorUniversity Hospital of Southern Denmark-
Autor(es): dc.contributorUniversity of Southern Denmark-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorMcGill University-
Autor(es): dc.contributorA. C. Camargo Cancer Center-
Autor(es): dc.contributorUniversidad Señor de Sipán-
Autor(es): dc.contributorBarretos Cancer Hospital-
Autor(es): dc.contributorDiagnósticos da América - DASA-
Autor(es): dc.contributorHospital Felicio Rocho-
Autor(es): dc.creatorCury, Sarah Santiloni-
Autor(es): dc.creatorKuasne, Hellen-
Autor(es): dc.creatorSouza, Jeferson dos Santos-
Autor(es): dc.creatorMuñoz, Juan Jose Moyano-
Autor(es): dc.creatorSilva, Jeyson Pereira da-
Autor(es): dc.creatorLopes, Ademar-
Autor(es): dc.creatorScapulatempo-Neto, Cristovam-
Autor(es): dc.creatorFaria, Eliney Ferreira-
Autor(es): dc.creatorDelaissé, Jean-Marie-
Autor(es): dc.creatorMarchi, Fabio Albuquerque-
Autor(es): dc.creatorRogatto, Silvia Regina-
Data de aceite: dc.date.accessioned2025-08-21T21:18:22Z-
Data de disponibilização: dc.date.available2025-08-21T21:18:22Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-07-19-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3389/fonc.2022.935093-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/240582-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/240582-
Descrição: dc.descriptionExtracellular matrix (ECM) remodeling and inflammation have been reported in penile carcinomas (PeCa). However, the cell types and cellular crosstalk involved in PeCa are unexplored. We aimed to characterize the complexity of cells and pathways involved in the tumor microenvironment (TME) in PeCa and propose target molecules associated with the TME. We first investigated the prognostic impact of cell types with a secretory profile to identify drug targets that modulate TME-enriched cells. The secretome analysis using the PeCa transcriptome revealed the enrichment of inflammation and extracellular matrix pathways. Twenty-three secreted factors were upregulated, mainly collagens and matrix metalloproteinases (MMPs). The deregulation of collagens and MMPs was confirmed by Quantitative reverse transcription - polymerase chain reaction (RT-qPCR). Further, the deconvolution method (digital cytometry) of the bulk samples revealed a high proportion of macrophages and dendritic cells (DCs) and B cells. Increased DCs and B cells were associated with better survival. A high proportion of cancer-associated fibroblasts (CAFs) was observed in low-survival patients. Patients with increased CAFs had decreased immune cell proportions. The treatment with the MMP inhibitor GM6001 in CAF cells derived from PeCa resulted in altered cell viability. We reported a crosstalk between immune cells and CAFs, and the proportion of these cell populations was associated with prognosis. We demonstrate that a drug targeting MMPs modulates CAFs, expanding the therapeutic options of PeCa.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionDepartment of Clinical Genetics University Hospital of Southern Denmark-
Descrição: dc.descriptionInstitute of Regional Health Research University of Southern Denmark-
Descrição: dc.descriptionDepartment of Structural and Functional Biology São Paulo State University (UNESP)-
Descrição: dc.descriptionRosalind and Morris Goodman Cancer Institute McGill University-
Descrição: dc.descriptionInternational Research Center (CIPE) A. C. Camargo Cancer Center-
Descrição: dc.descriptionUniversidad Señor de Sipán-
Descrição: dc.descriptionPelvic Surgery Department A. C. Camargo Cancer Center-
Descrição: dc.descriptionMolecular Oncology Research Center Barretos Cancer Hospital-
Descrição: dc.descriptionDepartment of Pathology Diagnósticos da América - DASA-
Descrição: dc.descriptionUro-oncology and Robotic Surgery Hospital Felicio Rocho-
Descrição: dc.descriptionClinical Cell Biology Lillebaelt Hospital University Hospital of Southern Denmark-
Descrição: dc.descriptionDepartment of Clinical Research Clinical Cell Biology University of Southern Denmark-
Descrição: dc.descriptionDepartment of Structural and Functional Biology São Paulo State University (UNESP)-
Idioma: dc.languageen-
Relação: dc.relationFrontiers in Oncology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectcancer-associated fibroblasts-
Palavras-chave: dc.subjectpenile cancer-
Palavras-chave: dc.subjectresponse to therapy-
Palavras-chave: dc.subjectsecretome-
Palavras-chave: dc.subjecttranscriptome-
Título: dc.titleInterplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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