Locopo N, Fanelli M, Gasparini G
Division of Medical Oncology, Azienda Ospedali Riuniti Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
Breast Cancer Res Treat. 1998;52(1-3):159-73. doi: 10.1023/a:1006175504673.
Growth, progression, and metastasis of breast cancer, as well as of most of the other tumors, are angiogenesis-dependent processes. Several pro-angiogenic growth factors and endogenous inhibitors of angiogenesis have been identified and sequenced, and experimental studies suggest that angiogenic activity of a tumor may result from downregulation of inhibitors of angiogenesis or up-regulation of endothelial growth factors. The mechanisms leading to the alteration of the balance between positive and negative modulators of angiogenesis are only partially known. We are at the beginning of research to identify the more active angiogenic factors in human breast cancer, and little information is presently available on their clinical significance. Preliminary results suggest that among the known angiogenic peptides, both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF/TP) have promising prognostic and, perhaps, predictive value. No data are available on the clinical value of co-determination of positive and negative regulators of angiogenesis to look at the angiogenic balance of each single tumor. Only a few studies have assessed the role of endogenous inhibitors of angiogenesis in human breast cancer, with results available only on thrombospondin-1 and -2 (TSP-1, -2). Finally, the determination of some integrins such as alpha6 and alphavbeta3 and of some other endothelial-adhesion molecules seems to be of potential prognostic value. Recognizing which are the more biologically active positive and negative angiogenic factors is the key for the identification not only of new prognostic markers but also of targets for antiangiogenic therapy in human breast cancer.
乳腺癌以及大多数其他肿瘤的生长、进展和转移均为血管生成依赖性过程。几种促血管生成生长因子和内源性血管生成抑制剂已被鉴定和测序，实验研究表明，肿瘤的血管生成活性可能源于血管生成抑制剂的下调或内皮生长因子的上调。导致血管生成正负调节因子之间平衡改变的机制仅部分为人所知。我们才刚刚开始研究以确定人类乳腺癌中更具活性的血管生成因子，目前关于它们的临床意义的信息很少。初步结果表明，在已知的血管生成肽中，血管内皮生长因子（VEGF）和血小板衍生的内皮细胞生长因子/胸苷磷酸化酶（PD-ECGF/TP）都具有良好的预后价值，或许还有预测价值。关于联合测定血管生成正负调节因子以了解单个肿瘤的血管生成平衡的临床价值，尚无相关数据。仅有少数研究评估了内源性血管生成抑制剂在人类乳腺癌中的作用，目前仅获得了关于血小板反应蛋白-1和-2（TSP-1、-2）的结果。最后，某些整合素如α6和αvβ3以及其他一些内皮黏附分子的测定似乎具有潜在的预后价值。识别哪些是更具生物活性的血管生成正负因子，不仅是识别人类乳腺癌新预后标志物的关键，也是抗血管生成治疗靶点的关键。
