Tumor-associated fibroblasts predominantly come from local and not circulating precursors

Significance Fibroblasts constitute an important element of tumors and have received considerable attention in recent years due to their tumor-promoting and immunosuppressive properties. As a consequence, tumor-associated fibroblasts (TAFs) are considered an attractive target for cancer therapies. However, their origin remains controversial, with some evidence pointing at a local origin, whereas many publications suggest a significant contribution of progenitors from bone marrow. We found that TAFs derive almost exclusively from local sources. Therefore, therapeutic strategies to target fibroblasts must exploit local recruitment and the unique transcriptional and response patterns of fibroblasts from different sites.