%0 Journal Article
%T Opposite effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) over-expression and knockdown on colorectal liver metastases
%A Obul R Bandapalli
%A Eva Paul
%A Peter Schirmacher
%A Karsten Brand
%J BMC Research Notes
%D 2012
%I BioMed Central
%R 10.1186/1756-0500-5-14
%X To address this paradox, we utilized the BALB/c/CT26 mouse model that reliably leads to liver metastasis after splenic tumor cell injection and variegated the type of target cells for therapeutic intervention and the modalities of gene transfer. Since we have observed before that over-expression of TIMP-1 in liver host cells leads to efficient tumor growth inhibition in this model, we now examined whether targeting the tumor cells themselves will have a similar effect.In concordance with the earlier results, TIMP-1 over-expression in tumor cells led to a dramatic reduction of tumor growth as well. To evaluate any influence of treatment modality, we further examined whether TIMP-1 knockdown in the same animal model would have the opposite effect on tumor growth than TIMP-1 over-expression. Indeed, TIMP-1 knockdown led to a marked increase in tumor burden.These data indicate that in the BALB/c/CT26 model, the modification of TIMP-1 has concordant effects irrespective of the type of target cell or the technique of modulation of TIMP-1 activity, and that TIMP-1 is unequivocally tumor inhibitory in this model.Colorectal carcinoma is the second most frequent cancer disease in both sexes [1]. For patients with this type of cancer, liver metastases are the main cause of death. They often remain the only manifestation of the disease once the primary tumor has been surgically removed [2,3].Therefore, successful treatment of liver metastases has the potential to cure the patient, and thus this is an area under intensive investigation. Besides standard treatment modalities like surgical intervention and chemotherapy, a number of molecular-based approaches for the treatment of colorectal liver metastases have been examined during the last 2 decades [4]. Among those, a modulation of the cancer cells' microenvironment has gained increasing interest [5-7], because a permissive host environment at the primary invasive site as well as at the site of metastasis is a prerequisite for s
%U http://www.biomedcentral.com/1756-0500/5/14