Title:
|
SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations
|
Author:
|
Mateo González, Francesca; Meca-Cortés, Oscar; 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.
|
Other authors:
|
Universitat de Barcelona |
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. |
Subject(s):
|
-Càncer de pròstata -Metàstasi -Marcadors tumorals -Prostate cancer -Metastasis -Tumor markers |
Rights:
|
cc-by (c) Mateo,F. et al., 2014
http://creativecommons.org/licenses/by/3.0/es |
Document type:
|
Article Article - Published version |
Published by:
|
BioMed Central
|
Share:
|
|