Monoclonal antibody 14C5 targets integrin αvβ3
Monoclonal antibody 14C5 targets integrin αvβ3
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DOI：
10.1158/1535-7163.mct-08-0600
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发表时间：
2008-12-01
影响因子：
5.7
通讯作者：
Slegers, Guido
中科院分区：
文献类型：
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作者：
Burvenich, Ingrid;Schoonooghe, Steve;Slegers, Guido
本研究鉴定并表征了单克隆抗体 (mAb) 14C5 识别的抗原。我们将抗原14C5的表达与八个整合素亚基（α（1），α（2），α（3），α（v），β（1），β（2），β（3）和β（4））和三个整合素异二聚体（α（v）β（3），α（v）β（5）和 α（5）β（1））通过流式细胞术。抗原 14C5 在八种不同的上皮癌细胞系（A549、A2058、C32、Capan-2、Colo 16、HT-1080、HT-29 和 SKBR-3）中显示出与 alpha(v)beta(5) 相似的表达。 mAb 14C5 阻断 P1F6（一种抗 alpha(v)beta(6) 特异性抗体）的特异性结合。在 14C5 阴性 Colo16 细胞中瞬时表达 alpha(v)beta(5) 后，mAb 14C5 能够结合 alpha(v)beta(5) 阳性细胞的亚群。我们评估了 14C5 抗原在结肠癌 (n = 20) 和肺癌 (n = 16) 癌组织中的组织分布。在分析的肿瘤中，50% 的结肠癌细胞呈 14C5 阳性，而支气管肺泡肺癌和典型类癌则不呈抗原阳性。更常见的非小细胞肺癌类型，即鳞状癌 (n = 5) 和腺癌 (n = 3)，在 5 例鳞状癌中的 2 例和所研究的 3 例腺癌中的 1 例中染色呈阳性。结肠癌（95%）和肺癌（50%）组织显示抗原14C5在肿瘤细胞周围的基质和邻近成纤维细胞的膜上广泛表达。我们首次证明 mAb 14C5 与血管整合素 α(v)beta(5) 结合，表明 mAb 14C5 可用作筛选剂来选择适合接受抗 α(v)beta(5) 疗法的结肠癌和肺癌患者。 [摩尔癌症疗法 2008;7(12):3771-9]
This study identifies and characterizes the antigen recognized by monoclonal antibody (mAb) 14C5. We compared the expression of antigen 14C5 with the expression of eight integrin subunits (alpha(1), alpha(2), alpha(3), alpha(v), beta(1), beta(2), beta(3), and beta(4)) and three integrin heterodimers (alpha(v)beta(3), alpha(v)beta(5), and alpha(5)beta(1)) by flow cytometry. Antigen 14C5 showed a similar expression to alpha(v)beta(5) in eight different epithelial cancer cell lines (A549, A2058, C32, Capan-2, Colo 16, HT-1080, HT-29, and SKBR-3). Specific binding of P1F6, an anti-alpha(v)beta(6) specific antibody, was blocked by mAb 14C5. After transient expression of alpha(v)beta(5) in 14C5-negative Colo16 cells, mAb 14C5 was able to bind a subpopulation of alpha(v)beta(5)-positive calls. We evaluated the tissue distribution of the 14C5 antigen in colon (n = 20) and lung (n = 16) cancer tissues, The colon carcinoma cells stained positive for 14C5 in 50% of tumors analyzed, whereas bronchoalveolar lung carcinoma and typical carcinoid were not positive for the antigen. More common types of non-small cell lung cancer, i.e., squamous (n = 5) and adenocarcinoma (n = 3), stained positive in 2 of 5 squamous carcinomas and in 1 of 3 investigated adenocarcinoma. Colon (95%) and lung (50%) carcinoma tissues showed extensive expression of antigen 14C5 in the stroma surrounding the tumor cells and on the membrane of the adjacent fibroblasts. We show for the first time that mAb 14C5 binds the vascular integrin alpha(v)beta(5), suggesting that mAb 14C5 can be used as a screening agent to select colon and lung cancer patients that are eligible for anti-alpha(v)beta(5)-based therapies. [Mol Cancer Ther 2008;7(12):3771-9]