Tokunaga Tetsuji, Abe Yoshiyuki, Tsuchida Takashi, Hatanaka Hiroyuki, Oshika Yoshiro, Tomisawa Masashi, Yoshimura Masumi, Ohnishi Yasuyuki, Kijima Hiroshi, Yamazaki Hitoshi, Ueyama Yoshito, Nakamura Masato
Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Int J Oncol. 2002 Nov;21(5):1027-32.
Stromal angiogenesis is an important factor for progression of malignant neoplasms. We used hammerhead ribozymes against vascular endothelial growth factor (VEGF) gene transcripts to down-regulate cell-associated VEGF189 isoform function in the pancreatic cancer cell line MIA PaCa2. MIA PaCa2 transfected with anti-VEGF189 ribozyme did not show any alteration of growth rate under tissue culture. When the transformants were subcutaneously transplanted, tumour volume of the ribozyme-transfected MIA PaCa2 xenografts was significantly smaller (P<0.01). No metastasis of MIA PaCa2 transfected with anti-VEGF189 was apparent, while disabled ribozyme-transfected MIA PaCa2 showed significant liver metastasis (P<0.05). These results suggested that VEGF189 plays an important role in growth and metastatic potential through alteration of angiogenic balance in cancer.
基质血管生成是恶性肿瘤进展的一个重要因素。我们使用针对血管内皮生长因子（VEGF）基因转录本的锤头状核酶来下调胰腺癌细胞系MIA PaCa2中细胞相关的VEGF189亚型功能。用抗VEGF189核酶转染的MIA PaCa2在组织培养条件下生长速率未显示任何改变。当将转化体皮下移植时，核酶转染的MIA PaCa2异种移植物的肿瘤体积显著更小（P<0.01）。抗VEGF189转染的MIA PaCa2未见转移，而转染失活核酶的MIA PaCa2则出现明显的肝转移（P<0.05）。这些结果表明，VEGF189通过改变癌症中的血管生成平衡在生长和转移潜能中发挥重要作用。
