Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.
OBJECTIVE
To explore the expression of heparanase gene, CD44v6, MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the clinicopathological factors.


METHODS
Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6, MMP-7 and nm23 protein in 43 human gastric carcinomas.


RESULTS
The expression of heparanase gene was positive in 29 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than those in adjacent normal gastric tissues (P<0.05). The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infiltration, lymph node metastasis and size of tumors (P<0.05), but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis (P>0.05). The positive rate of CD44v6, nm23 and MMP-7 proteins was 76.7%, 37.2% and 60.5%, respectively. The CD44v6 protein expression was significantly related to serosal infiltration, lymph node metastasis and TNM stage of disease (P<0.05). The nm23 protein expression was significantly related to the tumor gross appearance, lymph node and peritoneal metastasis (P<0.05). The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P<0.05). In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P<0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P<0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P>0.05), and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P>0.05).


CONCLUSIONS
Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas. However, co-detection of these factors may be important to predict metastatic spreading in such patients.
Chen
Jun-Qiang
JQ
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China. wzwk@gzsums.edu.cn
Zhan
Wen-Hua
WH
He
Yu-Long
YL
Peng
Jun-Sheng
JS
Wang
Jian-Ping
JP
Cai
Shi-Rong
SR
Ma
Jin-Ping
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary*; D005260:Female; D015870:Gene Expression; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D008875:Middle Aged; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness / Q000235:genetics; D009701:Nucleoside-Diphosphate Kinase; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D000099175:Heparanase
D005966:Glucuronidase; D018960:Hyaluronan Receptors; D020783:Matrix Metalloproteinase 7; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D020033:Protein Isoforms; D011506:Proteins; D000099175:Heparanase; C517938:NME1 protein, human