Davies M M, Mathur P, Carnochan P, Saini S, Allen-Mersh T G
Division of Surgery, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
Br J Cancer. 2002 Jan 7;86(1):123-9. doi: 10.1038/sj.bjc.6600020.
One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.
肿瘤血管生成与转移可能性之间临床关联的一种解释是，原发性肿瘤血管生成增加通过为肿瘤细胞侵入循环系统（血管内渗）提供更多机会，从而增强血行播散。我们设计了一种实验性肿瘤转移模型，该模型能够通过将原发性和转移性肿瘤部位分别暴露于血管生成剂的不同剂量来控制原发性肿瘤的血管生成。我们使用该模型评估血管生成剂碱性成纤维细胞生长因子水平的局部和全身升高对转移的影响。植入后肢K12/TR腺癌肿瘤的BDIX大鼠接受瘤内或全身碱性成纤维细胞生长因子或生理盐水注射。与注射生理盐水的对照组相比，瘤内和全身注射碱性成纤维细胞生长因子均导致肿瘤血管生成、血流量和生长显著增加，但肺转移并未增加。碱性成纤维细胞生长因子水平升高和原发性肿瘤血管生成增加并未增加转移。肿瘤血管生成与转移之间的临床关联很可能源于一种转移性肿瘤基因型，该基因型将肿瘤血管生成增加与更高的转移潜能联系起来。
