Scholarlink

Background <p><i>Secreted protein, acidic and rich in cysteine</i> (<i>SPARC</i>) may play an important role in tumor microenvironment (TME) contribution to metastasis, however molecular mechanism of <i>SPARC</i> contribution to TME remains elusive.</p> Experimental design <p>In this study, <i>SPARC</i> molecular status was explored for its clinical and functional relevance to metastasis in the context of its stromal overexpression, which may represent colorectal cancer (CRC) progression.</p> Results <p><i>SPARC</i> expression was highly specific to cancer stroma of CRC tumors (GSE35608) and exhibited prognostic relevance. <i>SPARC</i> knockdown (KD) in cancer-associated fibroblasts (CAFs) resulted in diminished metastatic phenotypes, accompanied by robust suppression of <i>COL1A1</i>/<i>COL3A1</i> expressions&#xa0;and multiple secretome genes. Among the secretome genes, <i>CSF1</i> was closely associated with stromal <i>SPARC</i> expression, and it was demonstrated that the <i>CSF1</i>/<i>CSF1R</i> axis was required for <i>SPARC</i>-induced cancer invasion. Comprehensive selection by stromal specificity and its <i>SPARC</i> association identified CAF-associated genes (CAFGs), including classical CAFs markers and COL family genes, which were uniquely enriched as higher priority for prognosis. These findings suggest that <i>SPARC</i>-mediated induction of COL family genes and secretome in the TME may be primarily featured against the host rather than be protective.</p> Conclusions <p>Our present findings may aid in simplifying molecular understanding of aggressive TME and enrich bona-fide therapeutic targets for cancer metastasis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

SPARC Induces COL1A1/COL3A1 Expressions Representing Aggressive Molecular Cancer-Associated Fibroblasts Signatures and CSF1-Mediated Cancer Invasion in Colorectal Cancer

  • 期刊论文

  • 发表日期：

    2025年8月20日

查看全文
  • Yusuke Nie,
  • Yoshiki Fujiyama,
  • Shumpei Shibaki,
  • Riku Okamoto,
  • Kota Okuno,
  • Keiko Oki,
  • Akiko Watanabe,
  • Yu Kuroda,
  • Takuya Goto,
  • Kazuko Yokota,
  • Keita Kojima,
  • Hiroki Harada,
  • Mikiko Kidachi,
  • Takafumi Soeno,
  • Mitsuo Yokota,
  • Takeshi Kaida,
  • Shuji Nakamoto,
  • Nobuyuki Nishizawa,
  • Hidefumi Kubo,
  • Hiroshi Tajima,
  • Takashi Kaizu,
  • Takahiro Yamanashi,
  • Masaki Nakamura,
  • Hidero Kitasato,
  • Tsutomu Yoshida,
  • Yoshiki Murakumo,
  • Makoto Saegusa,
  • Takafumi Sangai,
  • Naoki Hiki,
  • Takeshi Naitoh,
  • Yusuke Kumamoto,
  • Keishi Yamashita

摘要

Background

Secreted protein, acidic and rich in cysteine (SPARC) may play an important role in tumor microenvironment (TME) contribution to metastasis, however molecular mechanism of SPARC contribution to TME remains elusive.

Experimental design

In this study, SPARC molecular status was explored for its clinical and functional relevance to metastasis in the context of its stromal overexpression, which may represent colorectal cancer (CRC) progression.

Results

SPARC expression was highly specific to cancer stroma of CRC tumors (GSE35608) and exhibited prognostic relevance. SPARC knockdown (KD) in cancer-associated fibroblasts (CAFs) resulted in diminished metastatic phenotypes, accompanied by robust suppression of COL1A1/COL3A1 expressions and multiple secretome genes. Among the secretome genes, CSF1 was closely associated with stromal SPARC expression, and it was demonstrated that the CSF1/CSF1R axis was required for SPARC-induced cancer invasion. Comprehensive selection by stromal specificity and its SPARC association identified CAF-associated genes (CAFGs), including classical CAFs markers and COL family genes, which were uniquely enriched as higher priority for prognosis. These findings suggest that SPARC-mediated induction of COL family genes and secretome in the TME may be primarily featured against the host rather than be protective.

Conclusions

Our present findings may aid in simplifying molecular understanding of aggressive TME and enrich bona-fide therapeutic targets for cancer metastasis.