Andrade S P, Bakhle Y S, Hart I, Piper P J
Biology of Metastasis Laboratory, Imperial Cancer Research Fund, London, UK.
Br J Cancer. 1992 Nov;66(5):821-6. doi: 10.1038/bjc.1992.367.
The effects of tumour cells (Colon 26) on the development and response of new blood vessels to different vasoconstrictors (platelet activating factor; PAF, endothelin-1, angiotensin II, adrenalin and 5-hydroxytryptamine) have been investigated. Sponge implants in mice were used to host tumour cells while washout of 133Xe was employed to assess local blood flow in the implanted sponges. By 14 days after implantation the response of vessels in tumour-bearing implants to the various vasoconstrictors generally was decreased compared to that obtained in control sponge implants or adjacent normal skin. Thus at this time point the t1/2 for 133Xe washout from control sponges treated with adrenalin (0.5 micrograms) was 30 +/- 4 min whereas in tumour-bearing sponges it was 5 +/- 1 min. This decreased sensitivity in tumour vessels was probably not due to a complete lack of contractile elements since actin was demonstrated by immunohistochemistry around blood vessels in both types of implant. The results of the present study have shown that the pharmacological responses of blood vessels in a growing tumour, Colon 26, differed from the responses of vessels of a similar age in non-neoplastic tissue. These results appear to suggest that the different angiogenic stimuli released from tumour tissue may markedly influence pharmacological reactivity of newly formed blood vessels.
研究了肿瘤细胞(结肠26)对新生血管发育以及对不同血管收缩剂(血小板活化因子;PAF、内皮素-1、血管紧张素II、肾上腺素和5-羟色胺)反应的影响。在小鼠体内植入海绵以容纳肿瘤细胞,同时利用133Xe洗脱来评估植入海绵中的局部血流。植入后14天,与对照海绵植入物或相邻正常皮肤相比,荷瘤植入物中血管对各种血管收缩剂的反应普遍降低。因此,在这个时间点,用肾上腺素(0.5微克)处理的对照海绵中133Xe洗脱的t1/2为30±4分钟,而在荷瘤海绵中为5±1分钟。肿瘤血管中这种敏感性降低可能并非完全由于缺乏收缩元件,因为免疫组织化学显示两种植入物血管周围均有肌动蛋白。本研究结果表明,生长中的肿瘤(结肠26)血管的药理反应与非肿瘤组织中相同年龄血管的反应不同。这些结果似乎表明,肿瘤组织释放的不同血管生成刺激可能会显著影响新形成血管的药理反应性。