Isolation and characterization of patient-derived CNS metastasis-associated stromal cell lines

Ben Yi Tew1, Christophe Legendre2, Gerald C Gooden1,2

  • 1Department of Translational Genomics, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Oncogene
|February 1, 2019
PubMed

Insights

Researchers isolated and characterized CNS metastasis-associated stromal cells (cMASCs) from human tumors. These cMASCs showed tumor-inhibitory functions, restricting growth and inducing desmoplasia in vivo.

Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • The role of stromal cells within the tumor microenvironment of central nervous system (CNS) metastases is not well understood.
  • Stromal cells are crucial components of the tumor microenvironment, influencing tumor progression and treatment response.

Purpose of the Study:

  • To isolate and characterize human-derived stromal cells from CNS metastases (CM).
  • To investigate the functional role of these stromal cells in the context of CM.

Main Methods:

  • Generation of patient-derived cell lines (PDCs) from breast or lung CM.
  • Analysis of PDCs using DNA/RNA sequencing, DNA methylation profiling, and immunophenotypic assays.
  • In vivo functional analysis through co-implantation of stromal PDCs (termed cMASCs) with tumorigenic cells in mice.

Main Results:

  • cMASCs exhibited normal genotypes and molecular profiles resembling each other, suggesting a common origin.
  • Gene expression signatures indicated associations with cancer-associated fibroblasts (CAFs), epithelial-to-mesenchymal transition, and mesenchymal stem cells, with high collagen expression.
  • Functional assays revealed that cMASCs restricted tumor growth and induced desmoplasia in vivo.

Conclusions:

  • Human-derived CNS metastasis-associated stromal cells (cMASCs) were successfully isolated and characterized.
  • cMASCs possess tumor-inhibitory functions, potentially contributing to a protective host response against tumor growth in CNS metastases.
  • These findings highlight a novel stromal cell population with therapeutic potential in managing CNS metastases.

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