Involvement of bone marrow-derived stromal cells in gastrointestinal cancer development and metastasis

Background:  The involvement of bone marrow (BM) in tumor-stroma reactions or tumor development has not been examined in a cancer allograft, which has otherwise been appropriate for assessing therapeutic modalities. We investigated the fate of BM-derived cells in colon cancer allografts and liver metastases in mice. Methods:  C57BL/6 mice were irradiated and rescued by BM transplantation from green fluorescent protein (GFP)-transgenic mice. MC38 colon cancer cells were stably transfected with the pDsRed gene in order to identify tumor cells by fluorescence. These were inoculated into the mice to generate subcutaneous allografted tumors or liver metastases. The tumors were observed under confocal microscopy and fluorescent immunohistochemistry to determine the fate of tumor versus BM-derived cells. Results:  GFP-positive (GFP+) cells were consistently identified as vimentin+, α-smooth muscle actin (αSMA)+, spindle-shaped stromal cells in both the subcutaneous tumors and the liver metastases. GFP+ cells of leukocyte lineage also infiltrated the tumors. Neither GFP+ CD31+ endothelial cells nor GFP+ DsRed+ cells were detected in the tumor. Conclusions:  BM-derived cells frequently and consistently infiltrated the tumor allografts and metastases as interstitial cells and leukocytes. Cells derived from the fusion of BM cells and tumor cells were not observed. This model may be appropriate for the clarification of the effects of anticancer therapies and the study of BM-derived cells in tumor–host interactions.