A role for matrix metalloproteinases and tumor host interaction in hepatocellular carcinomas

Background: Hepatocellular carcinoma (HCC) occur in livers with injury-remodeling, accomplished by enzymes called matrix metalloproteinases (MMP). Metastasis involves basement membrane invasion also caused by MMP activity. Alterations in MMP expression and their endogenous inhibitor (TIMP) may factor in HCC metastasis. Methods: HCC specimens and lymph nodes (n = 7), and normal lymph tissue from organ donors (n = 8), were snap-frozen in liquid nitrogen and the mRNA precipitated. A series of reverse transcription-polymerase chain reactions (RT-PCR) were performed using MMP (MMP2, MMP7, MMP9) primers and TIMP (TIMP1, TIMP2) primers. These were semiquantitatively analyzed by comparing concentration with constitutive GADPH expression. Results: There is an increase in MMP2:TIMP2 mRNA expression ratio in the normal and tumor margin tissue compared to the tumor. There are increases in all MMP and TIMP mRNA expression (except TIMP1) and alterations in all of the MMP:TIMP expression ratios in the draining lymph node. Conclusions: Alterations exist in MMP2:TIMP2: expression at the margin, and all of the MMPs in the draining lymph nodes. This likely reflects a host-tumor interaction that regulates tumor metastasis.