Effects of Macrophage Metalloelastase on the Basic Fibroblast Growth Factor Expression and Tumor Angiogenesis in Murine Colon Cancer

Abstract

Previous studies have shown that overexpression of macrophage metalloelastase (MME) suppresses tumor growth in mice. The purpose of this study was to investigate the effects of MME on basic fibroblast growth factor (bFGF) expression and tumor angiogenesis in murine colon cancer. Murine CT-26 colon cancer cells stably transfected with MME were inoculated subcutaneously. Reverse-transcriptase polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry were used to explore the bFGF mRNA and protein expression. Immunohistochemical staining of CD34 was used to measure the microvessel density (MVD). bFGF mRNA levels in tumor tissues of CT-26-EGFP and nontransfected cells were respectively 2.7-fold (0.56 ± 0.063 vs. 0.21 ± 0.042) and 2.5-fold (0.53 ± 0.066 vs. 0.21 ± 0.042) higher than that in tumors of CT-26-EGFP-MME cells (p < 0.01). bFGF protein levels exhibited a similar trend. Tumors of CT-26-EGFP-MME cells demonstrated a lower microvessel density (9.35 ± 2.79) than control tumors of CT-26-EGFP cells (22.85 ± 3.80) and nontransfected cells (23.45 ± 4.49) (p < 0.001). We found that expression of MME inversely correlates with the expression of bFGF and tumor angiogenesis in a model of murine colon cancer. These data indicate that manipulation of MME expression could be a novel modality approach to colon cancer therapy.