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Background <p>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.</p> Methods <p>In this study, we examined the expression pattern and role of IGFBP2 in PCa cells and the stroma during prostate tumor cell progression.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月2日

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  • 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

摘要

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.