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Updated: Sep 10, 2025

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
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A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

Published on: January 22, 2021

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SPARC Induces COL1A1/COL3A1 Expressions Representing Aggressive Molecular Cancer-Associated Fibroblasts Signatures

Yusuke Nie1, Yoshiki Fujiyama1, Shumpei Shibaki1

  • 1Division of Advanced Surgical Oncology, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

Annals of Surgical Oncology
|August 20, 2025
PubMed
Abstract

Insights

Secreted protein, acidic and rich in cysteine (SPARC) promotes colorectal cancer metastasis by altering the tumor microenvironment (TME). Targeting SPARC and its associated genes offers potential therapeutic strategies for aggressive cancers.

Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • Secreted protein, acidic and rich in cysteine (SPARC) is implicated in tumor metastasis, but its precise role in the tumor microenvironment (TME) is not fully understood.
  • Stromal overexpression of SPARC may indicate colorectal cancer (CRC) progression.

Purpose of the Study:

  • To investigate the clinical and functional significance of SPARC in colorectal cancer (CRC) metastasis.
  • To elucidate the molecular mechanisms by which SPARC influences the tumor microenvironment (TME).

Main Methods:

  • Exploration of SPARC molecular status in CRC tumors.
  • SPARC knockdown in cancer-associated fibroblasts (CAFs).
  • Analysis of gene expression (COL1A1/COL3A1, secretome genes) and the CSF1/CSF1R axis.

Main Results:

  • SPARC expression is specific to CRC stroma and has prognostic value.
  • SPARC knockdown in CAFs reduced metastatic phenotypes and suppressed COL1A1/COL3A1 and secretome genes.
  • The CSF1/CSF1R axis is crucial for SPARC-driven cancer invasion.
  • CAF-associated genes (CAFGs), including COL genes, are prognostic indicators.

Conclusions:

  • SPARC promotes metastasis by inducing collagen and secretome genes in the TME, acting detrimentally to the host.
  • These findings enhance understanding of aggressive TME and identify potential therapeutic targets for cancer metastasis.
Keywords:
Cancer metastasisCytokineInterferonPrognosisSPARC

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