Brooks P C, Strömblad S, Klemke R, Visscher D, Sarkar F H, Cheresh D A
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
J Clin Invest. 1995 Oct;96(4):1815-22. doi: 10.1172/JCI118227.
Angiogenesis plays a fundamental role in human breast tumor progression. In fact, recent findings indicate that vascular density is a prognostic indicator of breast cancer disease status. Evidence is presented that the integrin alpha v beta 3 is not only a marker of human breast tumor-associated blood vessels, but that it plays a significant role in human angiogenesis and breast tumor growth. To assess the role of alpha v beta 3-dependent angiogenesis in the progression of human breast cancer, we examined a SCID mouse/human chimeric model with transplanted full thickness human skin containing alpha v beta 3-negative human breast tumor cells. This tumor induced a human angiogenic response as measured by vascular cell immunoreactivity with monoclonal antibodies LM609 and P2B1 directed to human alpha v beta 3 and CD31, respectively. Intravenous administration of LM609 either prevented tumor growth or markedly reduced tumor cell proliferation within the microenvironment of the human skin. These LM609-treated tumors not only contained significantly fewer human blood vessels but also appeared considerably less invasive than tumors in control animals. These findings demonstrate that alpha v beta 3 antagonists may provide an effective antiangiogenic approach for the treatment of human breast cancer.
血管生成在人类乳腺肿瘤进展中起着至关重要的作用。事实上，最近的研究结果表明，血管密度是乳腺癌疾病状态的一个预后指标。有证据表明，整合素αvβ3不仅是人类乳腺肿瘤相关血管的标志物，而且在人类血管生成和乳腺肿瘤生长中发挥着重要作用。为了评估αvβ3依赖性血管生成在人类乳腺癌进展中的作用，我们研究了一种SCID小鼠/人类嵌合模型，该模型移植了含有αvβ3阴性人类乳腺肿瘤细胞的全层人类皮肤。通过分别用针对人类αvβ3和CD31的单克隆抗体LM609和P2B1进行血管细胞免疫反应性测量，发现这种肿瘤诱导了人类血管生成反应。静脉注射LM609要么阻止了肿瘤生长，要么显著降低了人类皮肤微环境内的肿瘤细胞增殖。这些经LM609处理的肿瘤不仅含有的人类血管明显较少，而且与对照动物的肿瘤相比，侵袭性也明显较低。这些发现表明，αvβ3拮抗剂可能为治疗人类乳腺癌提供一种有效的抗血管生成方法。
