IGFBP2 alteration contributes to prostate cancer progression by modulating prostate stroma activation.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-10-02 DOI:10.1186/s12964-025-02414-6

Mingguo Huang, Shintaro Narita, Hiromi Sato, Yuya Sekine, Mizuki Kobayashi, Soki Kashima, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Kazuyuki Numakura, Mitsuru Saito, Hiroshi Nanjo, Takayuki Ikezoe, Tomonori Habuchi

{"title":"IGFBP2 alteration contributes to prostate cancer progression by modulating prostate stroma activation.","authors":"Mingguo Huang, Shintaro Narita, Hiromi Sato, Yuya Sekine, Mizuki Kobayashi, Soki Kashima, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Kazuyuki Numakura, Mitsuru Saito, Hiroshi Nanjo, Takayuki Ikezoe, Tomonori Habuchi","doi":"10.1186/s12964-025-02414-6","DOIUrl":null,"url":null,"abstract":"Background: Insulin-like growth factor (IGF) binding protein-2 (IGFBP2) is a secretory protein that modulate the activity of IGFs. It is highly expressed in various cancers such as prostate cancer (PCa), in which it may play a controversial role in tumor progression, however, the molecular mechanisms of IGFBP2 in PCa progression remain unclear.Methods: In this study, we examined the expression pattern and role of IGFBP2 in PCa cells and the stroma during prostate tumor cell progression.Results: IGFBP2 was highly expressed in LNCaP cells and prostate stromal fibroblasts (PrSC) and was mainly secreted by PrSCs. Tumor cell growth and invasiveness were not directly affected by treatment with IGFBP2 siRNAs (siIGFBP2) or recombinant IGFBP2 (rIGFBP2). However, decreased expression of IGFBP2 significantly increased PrSC activation and the secretion of pro-tumorigenic cytokines IL-6, IL-8, IP10, and CCL5 through upregulation of TGF-β, which subsequently enhanced prostate tumor cell progression. Clinically, low expression of stromal IGFBP2 was associated with a high reactive prostate stroma, advanced PCa progression, and increased IGFBP2 levels in the serum.Conclusion: Here, we provide mechanistic evidence that IGFBP2 act as a critical regulatory factor in the activation of prostate stromal microenvironment and contributes to aggressive PCa progression.","PeriodicalId":55268,"journal":{"name":"Cell Communication and Signaling","volume":"23 1","pages":"408"},"PeriodicalIF":8.2000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492507/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Communication and Signaling","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12964-025-02414-6","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Insulin-like growth factor (IGF) binding protein-2 (IGFBP2) is a secretory protein that modulate the activity of IGFs. It is highly expressed in various cancers such as prostate cancer (PCa), in which it may play a controversial role in tumor progression, however, the molecular mechanisms of IGFBP2 in PCa progression remain unclear.

Methods: In this study, we examined the expression pattern and role of IGFBP2 in PCa cells and the stroma during prostate tumor cell progression.

Results: IGFBP2 was highly expressed in LNCaP cells and prostate stromal fibroblasts (PrSC) and was mainly secreted by PrSCs. Tumor cell growth and invasiveness were not directly affected by treatment with IGFBP2 siRNAs (siIGFBP2) or recombinant IGFBP2 (rIGFBP2). However, decreased expression of IGFBP2 significantly increased PrSC activation and the secretion of pro-tumorigenic cytokines IL-6, IL-8, IP10, and CCL5 through upregulation of TGF-β, which subsequently enhanced prostate tumor cell progression. Clinically, low expression of stromal IGFBP2 was associated with a high reactive prostate stroma, advanced PCa progression, and increased IGFBP2 levels in the serum.

Conclusion: Here, we provide mechanistic evidence that IGFBP2 act as a critical regulatory factor in the activation of prostate stromal microenvironment and contributes to aggressive PCa progression.

查看原文本刊更多论文

IGFBP2改变通过调节前列腺基质激活促进前列腺癌进展。

背景：胰岛素样生长因子（IGF）结合蛋白-2 （IGFBP2）是调节IGF活性的分泌蛋白。IGFBP2在前列腺癌（PCa）等多种癌症中高表达，其在肿瘤进展中可能发挥有争议的作用，然而，IGFBP2在PCa进展中的分子机制尚不清楚。方法：本研究检测了IGFBP2在前列腺癌细胞和前列腺肿瘤细胞进展过程中的表达模式和作用。结果：IGFBP2在LNCaP细胞和前列腺间质成纤维细胞（PrSC）中高表达，主要由PrSC分泌。IGFBP2 sirna （siIGFBP2）或重组IGFBP2 （rIGFBP2）治疗对肿瘤细胞的生长和侵袭性没有直接影响。而IGFBP2的表达降低，通过上调TGF-β，显著增加PrSC的激活和促肿瘤细胞因子IL-6、IL-8、IP10、CCL5的分泌，从而促进前列腺肿瘤细胞的进展。在临床上，基质IGFBP2的低表达与高反应性前列腺基质、晚期前列腺癌进展和血清IGFBP2水平升高相关。结论：本研究提供了IGFBP2作为前列腺基质微环境激活的关键调控因子，促进前列腺癌侵袭性进展的机制证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.