Origin of carcinoma associated fibroblasts.

Recent evidence on the genomic integrity of non-malignant cells surrounding carcinoma cells has reinvigorated the discussion about the origin of the altered phenotype exhibited by carcinoma associated fibroblasts. Many hypotheses have been proposed for the origin of these altered cells, including standard connective tissue acute phase and stress response, fibroblast senescence, reciprocal interactions with the cancer cells, fibroblast specific somatic mutations, differentiation precursors and infiltrating mesenchymal stem cells. Here we review the definition of CAF phenotype and the evidence for each of those hypotheses, in the context of our current understanding of cancer etiology.