While cancer-associated fibroblasts (CAFs) are known to be a major constituent of the tumor microenvironment, their origin and roles in shaping disease initiation, progression and treatment response have remained unclear due to significant heterogeneity. Now, a research team led by Kristian Pietras from Lund University has discovered three distinct subpopulations of the cancer-associated fibroblasts.
Using a negative selection strategy combined with single-cell RNA sequencing of almost 770 transcriptomes of mesenchymal cells from a mouse model of breast cancer, the researchers managed to map and identify three subpopulations of CAFs: vascular fibroblasts, which control the development of blood vessels, matrix fibroblasts, which produce proteins that make the tumor stable and facilitate the migration of cells, and a third population which the researchers discovered to be actual tumor cells disguised as connective tissue cells. When investigating the subpopulations’ significance for breast cancer prognosis, they found that patients with a large number of vascular fibroblasts or matrix fibroblasts in their tumors had worse prognoses, as those cell types affect the development of metastases.
“We are convinced that more knowledge of the cellular structure of tumors and the function of communication between different cell types will enable us to find new ways to treat tumor diseases. In addition, measurements of the number of different connective tissue cells within a tumor can be developed to assess the risk of cancer recurrence in patients”, Kristian Pietras concludes in a press release from Lund University.
The Eukaryotic Single Cell Unit (ESCG) and National Bioinformatics Infrastructure (NBIS) at SciLifeLab supported the project through several steps in the process, with cell sorting, sequencing and bioinformatic analyses.
Read the full paper in Nature Communications
Read the press release from Lund University