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.
Abstract:
The functional role of human derived stromal cells in the tumor microenviornment of CNS metastases (CM) remain understudied. The purpose of the current study was to isolate and characterize stromal cells of the tumor microenvironment in CM. Four different patient-derived cell lines (PDCs) of stromal and one PDC of tumorigenic origin were generated from breast or lung CM. PDCs were analyzed by DNA/RNA sequencing, DNA methylation profiling, and immunophenotypic assays. The stromal derived PDCs were termed CNS metastasis-associated stromal cells (cMASCs). Functional analysis of cMASCs was tested by co-implanting them with tumorigenic cells in mice. cMASCs displayed normal genotypes compared with tumorigenic cell lines. RNA-seq and DNA methylation analyses demonstrated that cMASCs highly resembled each other, suggesting a common cell of origin. Additionally, cMASCs revealed gene expression signatures associated with cancer associated fibroblasts (CAFs), epithelial to mesenchymal transition, mesenchymal stem cells and expressed high levels of collagen. Functionally, cMASCs restricted tumor growth, and induced desmoplasia in vivo, suggesting that cMASCs may promote a protective host response to impede tumor growth. In summary, we demonstrated the isolation, molecular characterization and functional role of human derived cMASCs, a subpopulation of cells in the microenvironment of CM that have tumor inhibitory functions.
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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