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Title: SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations
Author: Mateo González, Francesca
Meca Cortés, Óscar
Celià Terrassa, Antoni
Fernández Amurgo, Yolanda
Abasolo, Ibane
Sánchez-Cid Pérez, Lourdes
Bermudo, Raquel
Sagasta, Amaia
Rodríguez-Carunchio, Leonardo
Pons, Mònica
Cánovas, Verónica
Marín Aguilera, Mercedes
Mengual Brichs, Lourdes
Alcaraz Asensio, Antonio
Schwartz Navarro, Simó
Mellado González, Begoña
Aguilera, Kristina Y.
Brekken, Rolf
Fernández Ruiz, Pedro Luis
Paciucci Barzanti, Rosanna
Thomsom, Timothy M.
Keywords: Càncer de pròstata
Marcadors tumorals
Prostate cancer
Tumor markers
Issue Date: 21-Oct-2014
Publisher: BioMed Central
Abstract: Background Tumor cell subpopulations can either compete with each other for nutrients and physical space within the tumor niche, or co-operate for enhanced survival, or replicative or metastatic capacities. Recently, we have described co-operative interactions between two clonal subpopulations derived from the PC-3 prostate cancer cell line, in which the invasiveness of a cancer stem cell (CSC)-enriched subpopulation (PC-3M, or M) is enhanced by a non-CSC subpopulation (PC-3S, or S), resulting in their accelerated metastatic dissemination. Methods M and S secretomes were compared by SILAC (Stable Isotope Labeling by Aminoacids in Cell Culture). Invasive potential in vitro of M cells was analyzed by Transwell-Matrigel assays. M cells were co-injected with S cells in the dorsal prostate of immunodeficient mice and monitored by bioluminescence for tumor growth and metastatic dissemination. SPARC levels were determined by immunohistochemistry and real-time RT-PCR in tumors and by ELISA in plasma from patients with metastatic or non-metastatic prostate cancer. Results Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. Of these, the protein most abundantly secreted in S relative to M cells was SPARC. Immunodepletion of SPARC inhibited the enhanced invasiveness of M induced by S conditioned medium. Knock down of SPARC in S cells abrogated the capacity of its conditioned medium to enhance the in vitro invasiveness of M cells and compromised their potential to boost the metastatic behavior of M cells in vivo. In most primary human prostate cancer samples, SPARC was expressed in the epithelial tumoral compartment of metastatic cases. Conclusions The matricellular protein SPARC, secreted by a prostate cancer clonal tumor cell subpopulation displaying non-CSC properties, is a critical mediator of paracrine effects exerted on a distinct tumor cell subpopulation enriched in CSC. This paracrine interaction results in an enhanced metastatic behavior of the CSC-enriched tumor subpopulation. SPARC is expressed in the neoplastic cells of primary prostate cancer samples from metastatic cases, and could thus constitute a tumor progression biomarker and a therapeutic target in advanced prostate cancer.
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It is part of: Molecular Cancer, 2014, vol. 13, num. 10, p. 237
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ISSN: 1476-4598
Appears in Collections:Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)

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