Effect of mouse macrophage metalloelastase gene transfer into murine CT-26 colon cancer ceils on orthotopic tumor growth and angiogenesis / 中华消化杂志

ABSTRACT

Objective To determine the correlation between mouse maerophage metalloelastase (MME)and vascular endothelial growth factor(VEGF)expression involved in angiogenesis of colon cancer.Methods A eDNA fragment coding for domainsⅠandⅡof MME was transfected into murine CT-26 colon cancer cells that were MME deficient.The enzymatic activity of recombinant MME was confirmed by cleavage of native substrate in vitro.An orthotopic implantation model was established by using MME-transfected cells and control cells.Tumor samples were subjected to in situ hybridization (ISH)and immunohistochemical staining(IHC)to detect expressions of MME and VEGF.The microvessel counting was used to assess angiogenesis of murine colon tumors.Results It was demon- strated that the tumor growth was significantly inhibited in MME-transfected group compared with pcDNA3.1 transfected and nontransfected groups(P＜0.001).It was also found that,compared with pcDNA3.1-transfected and nontransfected groups,the microvessel formation in MME transfected group was significantly reduced(P＜0.001).The expression of VEGF mRNA and protein was significantly lower in MME-transfected group than those in the controls,as demonstrated by ISH(MME-transfected group versus pcDNAa.1-transfected group,P=0.028;and versus nontransfected group,P=0.003) and by IHC(MME-transfected group versus pcDNA3.1-transfected group,P=0.025;and versus non- transfected group,P=0.008).Conclusions The MME gene transfected into murine colon cancer cells can effectively suppress the growth of orthotopic tumors by inhibition of vaseularity.Both MME and VEGF gene expression is highly associated with the vascularity of tumors,which may depend on a hal- ance between MME and VEGF expression.