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.
McKenna
Gregory J
GJ
Department of Surgery, Vancouver Hospital and Health Sciences Centre, University of British Columbia, 910 West 10th Ave., Vancouver, British Columbia, Canada V5Z 4E3.
Chen
Yongliang
Y
Smith
R Matt
RM
Meneghetti
Adam
A
Ong
Christopher
C
McMaster
Robert
R
Scudamore
Charles H
CH
Chung
Stephen W
SW
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000302:isolation & purification; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases