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Abstract：
Integrin α11β1 is a collagen receptor that has been reported to be overexpressed in the stroma of non-small cell lung cancer (NSCLC) and of head and neck squamous cell carcinoma (HNSCC). In the current study, we further analyzed integrin α11 expression in 14 tumor types by screening a tumor tissue array while using mAb 203E3, a newly developed monoclonal antibody to human α11. Different degrees of expression of integrin α11 were observed in the stroma of breast, ovary, skin, lung, uterus, stomach, and pancreatic ductal adenocarcinoma (PDAC) tumors. Co-expression queries with the myofibroblastic cancer-associated fibroblast (myCAF) marker, alpha smooth muscle actin (αSMA), demonstrated a moderate level of α11+ in myCAFs associated with PDAC and HNSCC tumors, and a lack of α11 expression in additional stromal cells (i.e., cells positive for fibroblast-specific protein 1 (FSP1) and NG2). The new function-blocking α11 antibody, mAb 203E1, inhibited cell adhesion to collagen I, partially hindered fibroblast-mediated collagen remodeling and obstructed the three-dimensional (3D) migration rates of PDAC myCAFs. Our data demonstrate that integrin α11 is expressed in a subset of non-pericyte-derived CAFs in a range of cancers and suggest that α11β1 constitutes an important receptor for collagen remodeling and CAF migration in the tumor microenvironment (TME).
摘要：
整合素α11β1是一种胶原蛋白受体，据报道在非小细胞肺癌（NSCLC）和头颈部鳞状细胞癌（HNSCC）的基质中过表达。在目前的研究中,我们通过使用新开发的抗人α11单克隆抗体mAb203E3筛选肿瘤组织阵列,进一步分析了14种肿瘤类型中整合素α11的表达.在乳腺间质中观察到整合素α11不同程度的表达,子房,皮肤,肺，子宫,胃,胰腺导管腺癌（PDAC）肿瘤。与肌纤维母细胞癌相关成纤维细胞（myCAF）标记的共表达查询，α平滑肌肌动蛋白（αSMA），在与PDAC和HNSCC肿瘤相关的myCAFs中显示出中等水平的α11+，以及在其他基质细胞中缺乏α11表达(即，成纤维细胞特异性蛋白1（FSP1）和NG2阳性的细胞。新的功能阻断α11抗体，mAb203E1，抑制细胞对胶原蛋白I的粘附，部分阻碍成纤维细胞介导的胶原蛋白重塑并阻碍PDACmyCAFs的三维（3D）迁移率。我们的数据表明，整联蛋白α11在一系列癌症中非周细胞衍生的CAF的子集中表达，并表明α11β1构成了肿瘤微环境（TME）中胶原蛋白重塑和CAF迁移的重要受体。
