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

• Published in: PloS one 2013-09, Vol.8 (9), p.e73666
• Main Authors: Xiao, Chuan-Xing, Wang, Huan-Huan, Shi, Ying, Li, Ping, Liu, Yun-Peng, Ren, Jian-Lin, Guleng, Bayasi
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Azoxymethane; B cells; Bone cancer; Bone marrow; Bone Marrow Cells - metabolism; Bone marrow transplantation; Bone Marrow Transplantation - methods; Cancer; Cancer research; Carcinogenesis; Carcinogens; CD11c antigen; CD11c Antigen - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; Cell Line; Chemokines; Colitis; Colitis - chemically induced; Colitis - metabolism; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - chemically induced; Colorectal Neoplasms - metabolism; Confocal microscopy; Cytometry; Dendritic cells; Dendritic Cells - metabolism; Dextran Sulfate; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Flow Cytometry; Fluorescence; Gastroenterology; Gastrointestinal diseases; Genetic engineering; Green fluorescent protein; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Health aspects; Health risks; Hospitals; Immune system; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Intestine; Laboratory animals; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Microscopy; Microscopy, Confocal; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Rodents; Stem cell transplantation; Stroma; T cells; Transgenic mice; Transplantation; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073666

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.