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Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features
Journal article   Open access   Peer reviewed

Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features

Qingxin Liu, Mike R Russell, Kristina Shahriari, Danielle L Jernigan, Mercedes I Lioni, Fernando U Garcia and Alessandro Fatatis
Cancer research (Chicago, Ill.), v 73(11), pp 3297-3305
01 Jun 2013
DOI: https://doi.org/10.1158/0008-5472.CAN-12-3970
PMID: 23536554
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1158/0008-5472.CAN-12-3970View
Published, Version of Record (VoR) Open

Abstract

NIH 3T3 Cells Prostatic Neoplasms - metabolism Up-Regulation Adenocarcinoma - pathology Humans Gene Expression Regulation, Neoplastic Bone Neoplasms - secondary Male Interleukin-1beta - genetics Bone Neoplasms - metabolism Adenocarcinoma - metabolism Heterografts Prostatic Neoplasms - genetics Neuroendocrine Cells - metabolism Adenocarcinoma - genetics Bone Neoplasms - genetics Interleukin-1beta - biosynthesis Carcinoma, Neuroendocrine - metabolism Prostatic Neoplasms - pathology Neuroendocrine Cells - pathology Receptor, Platelet-Derived Growth Factor alpha - metabolism Carcinoma, Neuroendocrine - genetics Disease Progression Animals Carcinoma, Neuroendocrine - pathology Receptor, Platelet-Derived Growth Factor alpha - genetics Synaptophysin - biosynthesis Cell Line, Tumor Mice Immunocompromised Host
Despite the progress made in the early detection and treatment of prostate adenocarcinoma, the metastatic lesions from this tumor are incurable. We used genome-wide expression analysis of human prostate cancer cells with different metastatic behavior in animal models to reveal that bone-tropic phenotypes upregulate three genes encoding for the cytokine interleukin-1β (IL-1β), the chemokine CXCL6 (GCP-2), and the protease inhibitor elafin (PI3). The Oncomine database revealed that these three genes are significantly upregulated in human prostate cancer versus normal tissue and correlate with Gleason scores ≥7. This correlation was further validated for IL-1β by immunodetection in prostate tissue arrays. Our study also shows that the exogenous overexpression of IL-1β in nonmetastatic cancer cells promotes their growth into large skeletal lesions in mice, whereas its knockdown significantly impairs the bone progression of highly metastatic cells. In addition, IL-1β secreted by metastatic cells induced the overexpression of COX-2 (PTGS2) in human bone mesenchymal cells treated with conditioned media from bone metastatic prostate cancer cells. Finally, we inspected human tissue specimens from skeletal metastases and detected prostate cancer cells positive for both IL-1β and synaptophysin while concurrently lacking prostate-specific antigen (PSA, KLK3) expression. Collectively, these findings indicate that IL-1β supports the skeletal colonization and metastatic progression of prostate cancer cells with an acquired neuroendocrine phenotype.

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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