During the last ten years, many research results have been referring to a particular type of cancer-associated fibroblasts associated with poor prognosis, invasiveness, metastasis and resistance to therapy in multiple cancer types, characterized by a gene expression signature with prominent presence of genes COL11A1, THBS2 and INHBA. Identifying the underlying biological mechanisms responsible for their creation may facilitate the discovery of targets for potential pan-cancer therapeutics. Using a novel computational approach for single-cell gene expression data analysis identifying the dominant cell populations in a sequence of samples from patients at various stages, we conclude that these fibroblasts are produced by a pan-cancer cellular transition originating from a particular type of adipose-derived stromal cells naturally present in the stromal vascular fraction of normal adipose tissue, having a characteristic gene expression signature. Focusing on a rich pancreatic cancer dataset, we provide a detailed description of the continuous modification of the gene expression profiles of cells as they transition from APOD-expressing adipose-derived stromal cells to COL11A1-expressing cancer-associated fibroblasts, identifying the key genes that participate in this transition. These results also provide an explanation to the well-known fact that the adipose microenvironment contributes to cancer progression.

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.