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Type: Artigo de periódico
Title: Secretome Profiling Of Oral Squamous Cell Carcinoma-associated Fibroblasts Reveals Organization And Disassembly Of Extracellular Matrix And Collagen Metabolic Process Signatures.
Author: Bagordakis, Elizabete
Sawazaki-Calone, Iris
Macedo, Carolina Carneiro Soares
Carnielli, Carolina M
de Oliveira, Carine Ervolino
Rodrigues, Priscila Campioni
Rangel, Ana Lucia C A
Dos Santos, Jean Nunes
Risteli, Juha
Graner, Edgard
Salo, Tuula
Leme, Adriana Franco Paes
Coletta, Ricardo D
Abstract: An important role has been attributed to cancer-associated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAF-secreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometry-based proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism. Among the upregulated proteins were fibronectin type III domain-containing 1 (FNDC1), serpin peptidase inhibitor type 1 (SERPINE1), and stanniocalcin 2 (STC2), the upregulation of which was validated by quantitative PCR and ELISA in an independent set of CAF cell lines. The transition of transforming growth factor beta 1 (TGF-β1)-mediating NOFs into CAFs was accompanied by significant upregulation of FNDC1, SERPINE1, and STC2, confirming the participation of these proteins in the CAF-derived secretome. Type I collagen, the main constituent of the connective tissue, was also associated with several upregulated biological processes. The immunoexpression of type I collagen N-terminal propeptide (PINP) was significantly correlated in vivo with CAFs in the tumor front and was associated with significantly shortened survival of OSCC patients. Presence of CAFs in the tumor stroma was also an independent prognostic factor for OSCC disease-free survival. These results demonstrate the value of secretome profiling for evaluating the role of CAFs in the tumor microenvironment and identify potential novel therapeutic targets such as FNDC1, SERPINE1, and STC2. Furthermore, type I collagen expression by CAFs, represented by PINP levels, may be a prognostic marker of OSCC outcome.
Subject: Cancer-associated Fibroblasts
Extracellular Matrix
Type I Collagen
Rights: fechado
Identifier DOI: 10.1007/s13277-015-4629-y
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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