Sckell A, Safabakhsh N, Dellian M, Jain R K
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Cancer Res. 1998 Dec 15;58(24):5866-9.
Some primary tumors are capable of suppressing the growth of their metastases by presumably generating antiangiogenic factors such as angiostatin. We hypothesized that the amount of inhibitor(s) released by a tumor increases with tumor growth. We tested this hypothesis by evaluating the relationship between the size of a primary tumor and its ability to inhibit angiogenesis at a secondary site. Furthermore, we characterized the effects of the primary tumor on physiological properties of newly formed vessels at the secondary site. Angiogenesis and physiological properties were measured using intravital microscopy of angiogenic vessels in the gels containing basic fibroblast growth factor placed into cranial windows of immunodeficient mice bearing human prostatic carcinoma (PC-3) in their flank. The PC-3 tumor inhibited angiogenesis in the gels, and surgical resection of tumor reversed this inhibition. The inhibition of angiogenesis 20 days after gel implantation (range, 0-83%) correlated positively (r = 0.625; P < 0.008) with the tumor size on the day of gel implantation (range, 19-980 mm3). The primary tumor also suppressed leukocyte-adhesion in angiogenic vessels, thus helping them evade the immune recognition. These results provide an additional rationale for combining antiangiogenic treatment with local therapies.
一些原发性肿瘤可能通过产生抗血管生成因子（如血管抑素）来抑制其转移灶的生长。我们推测肿瘤释放的抑制剂数量会随着肿瘤生长而增加。我们通过评估原发性肿瘤大小与其抑制继发部位血管生成能力之间的关系来验证这一假设。此外，我们还研究了原发性肿瘤对继发部位新生血管生理特性的影响。采用活体显微镜观察，在携带人前列腺癌（PC-3）的免疫缺陷小鼠侧腹颅骨窗内植入含有碱性成纤维细胞生长因子的凝胶，以此来测量血管生成和生理特性。PC-3肿瘤抑制了凝胶中的血管生成，手术切除肿瘤可逆转这种抑制作用。凝胶植入20天后血管生成的抑制率（范围为0 - 83%）与凝胶植入当天的肿瘤大小（范围为19 - 980 mm³）呈正相关（r = 0.625；P < 0.008）。原发性肿瘤还抑制了血管生成血管中的白细胞黏附，从而帮助它们逃避免疫识别。这些结果为抗血管生成治疗与局部治疗相结合提供了额外的理论依据。
