Vascular endothelial growth factor and enhanced angiogenesis do not promote metastatic conversion of a newly established azoxymethane-induced colon cancer cell line.
The organo-specific carcinogen, azoxymethane (AOM), produces colon tumors in mice that share many pathological features with sporadic human colorectal cancer (CRC). An important distinction between AOM-induced CRC and human CRC is lack of mucosal invasion in the murine model. To assess the role of the microenvironment in preventing the invasive phenotype, multiple benign in situ adenocarcinomas were harvested from AOM-treated mice and cultured in vitro. However, tumor cell growth was extremely limiting under standard culturing conditions. Thus, we injected tumor cells directly into nude mice and performed two serial transplants, and successfully explanted a rapidly growing epithelial tumor cell line (AJ02nm(0)). When injected subcutaneously (sc) into nude mice, AJ02nm(0) cells formed well-differentiated adenocarcinomas with minimal tumor invasive capacity. To define whether metastatic and invasive potential were related to lack of angiogenic stimuli, the AJ02nm(0) cells were transfected to overexpress murine vascular endothelial growth factor-164 (VEGF(164)). AJ02nm-VEGF cells produced rapidly growing tumors in nude mice that exhibited extensive pseudo-epithelial ductal architecture and supporting vasculature, but without increased invasive potential compared to controls. The established murine colon epithelial cell line provides a useful experimental model to further elaborate genetic and epigenetic factors that may promote or inhibit colon tumorigenesis and metastasis.
Belinsky
Glenn S
GS
Center for Molecular Medicine, School of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030-3101, USA.
Claffey
Kevin P
KP
Nambiar
Prashant R
PR
Guda
Kishore
K
Rosenberg
Daniel W
DW
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000473:pathology; D007621:Karyotyping; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A