The role of gelatinase in hepatic metastasis of colorectal cancer.
OBJECTIVE
To determine the role of gelatinase in the hepatic metastatic process of colorectal cancer, we correlated gelatinolytic activity in colorectal tumor tissue both to the presence of intravasated colorectal epithelial cells and to the formation of liver metastasis.


METHODS
The gelatinolytic activity was analyzed in tumor tissue samples from 68 colorectal cancer patients by using gelatin substrate zymography. The presence of intravasated colorectal epithelial cells was defined as detection of guanylyl cyclase C mRNA in blood sampled from drainage vein of a tumor-bearing colorectal segment.


RESULTS
Forty of 68 patients were noted to have guanylyl cyclase C mRNA expression in their drainage venous blood. Fifteen patients were noted to have liver metastasis at the time of surgery, and another 15 patients developed liver metastasis during median follow-up period of 53 months. Either individual or total gelatinolytic activity in colorectal tumor tissue failed to predict the presence of intravasated colorectal epithelial cells in the drainage venous blood or formation of liver metastasis. Presence of both intravasated colorectal epithelial cells and high total gelatinolytic activity in colorectal tumor tissue, however, is a strong predictor of liver metastasis (P = 0.004).


CONCLUSIONS
Our data suggested that gelatinolytic activity in colorectal tumor tissues may facilitate the hepatic metastatic process in the steps after intravasation but not during or before intravasation.
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan 10002, Republic of China.
Yu-Wen
YW
Tien
Po-Huang
PH
Lee
Rey-Heng
RH
Hu
Su-Ming
SM
Hsu
King-Jen
KJ
Chang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D005260:Female; D018093:Gelatinases / Q000378:metabolism / Q000502:physiology*; D006162:Guanylate Cyclase / Q000096:biosynthesis / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome
D012333:RNA, Messenger; D018000:Receptors, Peptide; D012313:RNA; D018093:Gelatinases; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled