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Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
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Asporin Restricts Mesenchymal Stromal Cell Differentiation, Alters the Tumor Microenvironment, and Drives Metastatic

Robert M Hughes1,2,3, Brian W Simons1, Hamda Khan1,2,3

  • 1The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, Baltimore, Maryland.

Cancer Research
|May 25, 2019
PubMed

Insights

Asporin (ASPN), a factor from mesenchymal stromal cells (MSCs), drives tumor metastasis by altering the tumor microenvironment. Blocking ASPN reduces metastasis and impacts tumor-associated cells.

Area of Science:

  • Oncology
  • Cell Biology
  • Tumor Microenvironment Research

Background:

  • Tumor metastasis involves complex interactions within the tumor microenvironment, not just cancer cells.
  • Mesenchymal stromal cells (MSCs) are key components of this microenvironment, influencing tumor progression.

Purpose of the Study:

  • To identify novel factors secreted by MSCs that regulate metastatic development.
  • To elucidate the role of asporin (ASPN) in the tumor microenvironment and its impact on metastasis.

Main Methods:

  • Investigated ASPN expression in MSCs and its correlation with differentiation.
  • Utilized ASPN-null mice to assess the in vivo impact of ASPN on prostate tumor growth and metastasis.
  • Analyzed tumor microenvironment composition, including MSCs, cancer stem cells, vasculature, and immune cells.

Main Results:

  • ASPN is highly expressed in MSCs and regulates their self-renewal and differentiation.
  • Secreted ASPN binds BMP-4, inhibiting MSC differentiation.
  • ASPN expression is conserved in cancer-associated fibroblasts (CAFs).
  • ASPN-null mice exhibited reduced tumor-associated MSCs, fewer cancer stem cells, decreased vasculature, and increased CD8+ T cells.
  • ASPN deficiency significantly reduced lung metastases in prostate tumor models.

Conclusions:

  • Asporin (ASPN) is a critical secreted factor from mesenchymal stromal cells (MSCs) that promotes tumor metastatic progression.
  • ASPN extensively modulates the tumor microenvironment, affecting multiple cell types and promoting metastasis.
  • Targeting ASPN may represent a novel therapeutic strategy to inhibit cancer metastasis.

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