Sakate Yoji, Yashiro Masakazu, Tanaka Hiroaki, Sunami Tsuyoshi, Kosaka Kinshi, Hirakawa Kosei
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
J Surg Res. 2004 Nov;122(1):89-95. doi: 10.1016/j.jss.2004.06.011.
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.
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.
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.
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.
淋巴结转移是胃癌关键的预后因素之一。我们曾报道，ICAM - 1基因转染对胃癌淋巴结转移有效。共刺激因子之一的B7 - 1，在使用黑色素瘤和膀胱癌细胞系时，与ICAM - 1一样，据报道可诱导细胞毒性T淋巴细胞。在本研究中，我们通过将B7 - 1基因转染至胃癌细胞，研究了B7 - 1对淋巴结转移的抑制作用。
我们将B7 - 1基因转染至胃癌细胞系（OCUM - 2MLN），并分析B7 - 1转导对淋巴结转移的影响、单核淋巴细胞对癌细胞的体外黏附性和细胞毒性测定，以及胃癌细胞原位植入体内后的淋巴结转移能力。
我们发现，单核淋巴细胞对B7 - 1转染细胞（2MLN/B7）的黏附性和细胞毒性明显强于其亲本OCUM - 2MLN细胞。在裸鼠中，2MLN/B7异种移植瘤的肿瘤生长速度明显慢于OCUM - 2MLN异种移植瘤。在裸鼠原位植入实验中，胃内的2MLN/B7细胞发生的淋巴结转移明显少于OCUM - 2MLN细胞。组织学结果显示，白细胞在2MLN/B7肿瘤及其转移灶中均有密集浸润，然而，在与2MLN细胞相关的病灶中几乎未观察到。
B7 - 1可能通过增强免疫原性机制在抑制淋巴结转移中发挥重要作用，且B7 - 1基因转导可能对胃癌淋巴结转移有效。
