Distribution of bone-marrow-derived endothelial and immune cells in a murine colitis-associated colorectal cancer model.

Abstract

Inflammatory bowel disease (IBD) can lead to an increased risk of developing colorectal cancer (CRC). The aim of this study was to establish a model for combined bone marrow transplantation (BMT) and colitis-associated colorectal cancer (CAC) and to define the contribution of BM-derived cells during the inflammation associated with carcinogenesis. We established a model for BMT using green fluorescent protein (GFP) transgenic mice, followed by AOM/DSS-induced CAC, and performed confocal microscopy analysis on in vivo living tissue and frozen tumor sections. Our imaging analyses showed that GFP-positive cells extensively infiltrated the tumor stroma and that some WGA and GFP or CD31 and GFP double-positive cells were observed in the lining of tumor vessels. Flow cytometry analysis of the tumor-infiltrating cells showed that the GFP-positive CD11c+ DCs cells were one-third of the GFP+/CD11C- cells, and that half of these DCs (0.96% vs 1.02%) were GFP-positive BM-derived cells. The majority of CD4(+) T cells were GFP-negative (12.02% vs 1.9%), and we discovered a novel CD4(+) CD11c(+) DC subset (0.34% vs 1.64%). In conclusion, we defined the distribution of BM-derived endothelial cells, CD11c(+) DCs and CD4(+) T cells in tumors. This model might be useful for elucidating the diverse BM-derived cell types and functions during the progression of colitis-associated colorectal cancer.