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

Autor:	Cury SS; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.; Department of Structural and Functional Biology, São Paulo State University (UNESP), Botucatu, Brazil., Kuasne H; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Denmark.; Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada.; International Research Center (CIPE), A. C. Camargo Cancer Center, São Paulo, Brazil., Souza JDS; Department of Structural and Functional Biology, São Paulo State University (UNESP), Botucatu, Brazil., Muñoz JJM; International Research Center (CIPE), A. C. Camargo Cancer Center, São Paulo, Brazil.; Universidad Señor de Sipán, Chiclayo, Peru., da Silva JP; International Research Center (CIPE), A. C. Camargo Cancer Center, São Paulo, Brazil., Lopes A; Pelvic Surgery Department, A. C. Camargo Cancer Center, São Paulo, Brazil., Scapulatempo-Neto C; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Department of Pathology, Diagnósticos da América - DASA, Barueri, Brazil., Faria EF; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.; Uro-oncology and Robotic Surgery, Hospital Felicio Rocho, Belo Horizonte, Brazil., Delaissé JM; Clinical Cell Biology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark.; Department of Clinical Research, Clinical Cell Biology, University of Southern Denmark, Odense, Denmark., Marchi FA; International Research Center (CIPE), A. C. Camargo Cancer Center, São Paulo, Brazil., Rogatto SR; Department of Clinical Genetics, University Hospital of Southern Denmark, Vejle, Denmark.; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Jul 19; Vol. 12, pp. 935093. Date of Electronic Publication: 2022 Jul 19 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.935093
Abstrakt:	Extracellular 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Cury, Kuasne, Souza, Muñoz, da Silva, Lopes, Scapulatempo-Neto, Faria, Delaissé, Marchi and Rogatto.)
Databáze:	MEDLINE
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