Usefulness of inhibiting the lymph node metastasis in human gastric carcinoma by B7-1 gene transfection.
BACKGROUND
Lymph node metastasis is one of the crucial prognostic factors in gastric cancer. We have reported that ICAM-1 gene transfection was effective against lymph node metastases of gastric cancer. B7-1, one of the co-stimulatory factors, was reported to induce cytotoxic T lymphocytes when using melanoma and bladder cancer cell lines, as well as ICAM-1. In this study, we investigated the inhibitory effect of B7-1 on lymph node metastasis by B7-1 gene transfection into gastric cancer cells.


METHODS
We transfected B7-1 genes into a gastric cancer cell line (OCUM-2MLN) and analyzed the effect of B7-1 transduction on lymph node metastasis, the in vitro adhesiveness and cytotoxicity assay of mononuclear lymphocytes to cancer cells and lymph node metastatic ability after orthotopic implantation of gastric cancer cells in vivo.


RESULTS
We revealed that mononuclear lymphocytes showed significantly stronger adherence and cytotoxicity to B7-1 transfected cells (2MLN/B7) than its parent OCUM-2MLN cells. The tumor growth rate of 2MLN/B7 xenograft was significantly slower than OCUM-2MLN xenograft in nude mice. In orthotopic implantation experiments for nude mice, 2MLN/B7 cells in stomach developed significantly less lymph node metastasis than OCUM-2MLN cells. Histologic findings showed that leukocytes were intensively infiltrated in both the 2MLN/B7 tumors and its metastatic lesions, however, were scarcely observed in the lesions associated with 2MLN cells.


CONCLUSIONS
B7-1 may play an important role in inhibiting lymph node metastasis by the mechanism of enhanced immunogenicity, and that B7-1 gene transduction might be effective against lymph node metastases of gastric cancer.
Sakate
Yoji
Y
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Yashiro
Masakazu
M
Tanaka
Hiroaki
H
Sunami
Tsuyoshi
T
Kosaka
Kinshi
K
Hirakawa
Kosei
K
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D014183:Transplantation, Heterologous
D000906:Antibodies; D018122:B7-1 Antigen