Expression of MMP-7 and MT1-MMP in peritoneal dissemination of gastric cancer.
OBJECTIVE
In this study, we examined the expression of MMP-2, MMP-7, and MT1-MMP in peritoneal dissemination of gastric cancer, so as to clarify a possible role of these MMPs in developing peritoneal dissemination, using culture cells and an animal model with peritoneal dissemination.


METHODS
Total RNA was extracted from tumor tissues of disseminated foci from 7 patients with gastric cancer and human gastric cancer cell lines of STSA, STKM-1, MKN-28, MKN-45, and KATOIII. Expressions of mRNA for MMP-2, MMP-7, and MT1-MMP were analyzed by reverse transcriptase-polymerase chain reaction. To examine relationships between the expression of these mRNAs and the ability to establish peritoneal dissemination, nude mice were injected into the intraperitoneal cavity with 106 cultured cells of those 5 gastric cancer cell lines.


RESULTS
MMP-7 was expressed in 6 of 7 tissues (85.7%) and MT1-MMP in 2 of 7 tissues (28.6%), while MMP-2 was not detected in any of 7 tumor tissues. All 7 tumors had either MMP-7 or MT1-MMP. MMP-7 was recognized in 4 of 5 cells (80%) and MT1-MMP in 2 of 5 cells (40%), while MMP-2 was not found at all. All 5 cancer cells expressed at least one MMP mRNA. In the animal experiments, nude mice inoculated with STKM-1 or MKN-45 cells developed peritoneal dissemination, while those with other cell lines did not. MMP-7 was found both in STSA and MKN-28 (dissemination negative), and in STKM-1 and MKN-45 (dissemination positive). MT1-MMP mRNA was detected in one of two dissemination positive cell lines and in one of three dissemination negative ones.


CONCLUSIONS
Our results suggested the importance of MMP-7 and MT1-MMP in the peritoneal metastases of gastric cancer, however, it has to be further dissected what role these MMPs might play in detaching of cancer cells from the gastric wall and establishing peritoneal disseminating foci.
Yoshikawa
Takaki
T
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama Kowan Hospital, Yokohama, Japan. yoshika@yc5.so-net.ne.jp
Yanoma
Shunsuke
S
Tsuburaya
Akira
A
Kobayashi
Osamu
O
Sairenji
Motonori
M
Motohashi
Hisahiko
H
Miyagi
Yohei
Y
Morinaga
Soichiro
S
Noguchi
Yoshikazu
Y
Yamamoto
Yuji
Y
D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000201:enzymology* / Q000556:secondary*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*
D012333:RNA, Messenger; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14