FGF23 promotes prostate cancer progression.

Shu Feng,Michael Ittmann,Jianghua Wang,Chad J Creighton,Yiqun Zhang

doi:10.18632/oncotarget.4174

Shu Feng, Michael Ittmann + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.4174

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Abstract

Prostate cancer is the most common cancer in US men and the second leading cause of cancer deaths. Fibroblast growth factor 23 (FGF23) is an endocrine FGF, normally expressed by osteocytes, which plays a critical role in phosphate homeostasis via a feedback loop involving the kidney and vitamin D. We now show that FGF23 is expressed as an autocrine growth factor in all prostate cancer cell lines tested and is present at increased levels in prostate cancer tissues. Exogenous FGF23 enhances proliferation, invasion and anchorage independent growth in vitro while FGF23 knockdown in prostate cancer cell lines decreases these phenotypes. FGF23 knockdown also decreases tumor growth in vivo. Given that classical FGFs and FGF19 are also increased in prostate cancer, we analyzed expression microarrays hybridized with RNAs from of LNCaP cells stimulated with FGF2, FGF19 or FGF23. The different FGF ligands induce overlapping as well as unique patterns of gene expression changes and thus are not redundant. We identified multiple genes whose expression is altered by FGF23 that are associated with prostate cancer initiation and progression. Thus FGF23 can potentially also act as an autocrine, paracrine and/or endocrine growth factor in prostate cancer that can promote prostate cancer progression.

Highlights

Prostate cancer (PCa) is the most common visceral malignancy and the second leading cause of cancer deaths in men in the United States
Fibroblast growth factor 23 (FGF23) is a circulating endocrine fibroblast growth factor (FGF) that plays a critical role in calcium and phosphate homeostasis
We show that FGF23 is expressed as an autocrine growth factor expressed in all PCa cell lines tested that promotes the transformed phenotype, based on both in vitro and in vivo studies

Summary

INTRODUCTION

Prostate cancer (PCa) is the most common visceral malignancy and the second leading cause of cancer deaths in men in the United States. Aberrant FGF signaling can promote tumor development by directly driving cancer cell proliferation, invasion and survival as well as by supporting tumor angiogenesis [1,2,3,4,5,6,7,8,9,10]. These observations make FGF signaling networks increasingly attractive as targets for therapeutic intervention in cancer. We show that FGF23 can act as an endocrine, paracrine and/ or aurocrine growth factor in PCa and plays an important role in PCa progression

RESULTS

DISCUSSION

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MATERIALS AND METHODS