Single-cell RNA-seq analysis reveals the pan-cancer transformation of adipose-derived stromal cells into COL11A1-expressing metastasis-associated fibroblasts

During the last ten years, many research results have been referring to a particular type of cancer-associated fibroblasts associated with invasiveness, metastasis and resistance to therapy, present in nearly identical form in many individual types of solid cancer. These fibroblasts are characterized by the expression of several genes, prominent among them COL11A1, THBS2, and INHBA. Identifying the origin of this universal metastasis-associated fibroblastic cell population and the underlying biological mechanisms responsible for their creation may help towards the identification of drug targets for pan-cancer metastasis-inhibiting therapeutics. This information, however, remains elusive. We have performed an extensive computational analysis of single-cell gene expression data from many cancer types, concluding that these fibroblasts are produced by a cancer-associated transformation of naturally occurring normal adipose-derived stromal cells. Focusing on a rich pancreatic cancer dataset, we also provide a detailed description of the continuous modification of the gene expression profile of the fibroblastic population as they transition from APOD-expressing adipose-derived stromal cells to COL11A1-expressing metastasis-associated fibroblasts, identifying the key genes that participate in this transformation.