ANTIINTEGRIN ALPHA-V-BETA-3 BLOCKS HUMAN BREAST-CANCER GROWTH AND ANGIOGENESIS IN HUMAN SKIN
ANTIINTEGRIN ALPHA-V-BETA-3 BLOCKS HUMAN BREAST-CANCER GROWTH AND ANGIOGENESIS IN HUMAN SKIN
复制标题
DOI：
10.1172/jci118227
复制
发表时间：
1995-10-01
影响因子：
15.9
通讯作者：
CHERESH, DA
中科院分区：
文献类型：
--
作者：
BROOKS, PC;STROMBLAD, S;CHERESH, DA
血管生成在人类乳腺肿瘤的发展中起着重要的作用，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预后指标，证据表明整合素α v β 3不仅是人类乳腺肿瘤相关血管的标志物，而且它在人类血管生成和乳腺肿瘤生长中起着重要作用。为了评估α v β 3依赖性血管生成在人乳腺癌进展中的作用，我们检查了移植了含有α v β 3阴性人乳腺肿瘤细胞的全厚度人皮肤的SCID小鼠/人嵌合模型，该肿瘤诱导人血管生成反应，如通过血管细胞免疫反应性用针对人α v β 3和CD 31的单克隆抗体LM 609和P2 B1测量的，静脉内施用LM 609防止了肿瘤生长或显著降低了人皮肤微环境中的肿瘤细胞增殖。这些LM 609处理的肿瘤不仅含有显著更少的人血管，而且与对照动物中的肿瘤相比，侵袭性明显更低。这些发现表明，α v β 3拮抗剂可能为治疗人乳腺癌提供有效的抗血管生成方法。
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.