Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts.

The role of myofibroblasts in tissue repair and fibrosis is well documented, but the source of these myofibroblasts is unclear. There is evidence of a circulating population of fibrocytes that can home to areas of injury and contribute to myofibroblast populations. Previously, we have shown that the bone marrow is a source of myofibroblasts for many tissues including the gut, lung, and kidney and that this phenomenon is exacerbated by injury. We now show that the bone marrow can contribute to myofibroblast and fibroblast populations in tumor stroma in a mouse model of pancreatic insulinoma. Mice transgenic for the rat insulin promoter II gene linked to the large-T antigen of SV40 (RIPTag) develop solid beta-cell tumors of the pancreas. Approximately 25% of myofibroblasts in these pancreatic tumors were donor-derived, and these were concentrated toward the edge of the tumor. Thus, the development of tumor stroma is at least in part a systemic response that may ultimately yield methods of targeting new therapy.