采用人重组 SIP 格式抗体对肿瘤血管中存在的癌胚型纤维连接蛋白和 tenascin-C 进行对比分析。

A comparative analysis of oncofetal fibronectin and tenascin-C incorporation in tumour vessels using human recombinant SIP format antibodies.

机构信息

Institute of Pathology, University Hospital Jena, Ziegelmühlenweg 1, 07743, Jena, Germany.

出版信息

Histochem Cell Biol. 2010 Apr;133(4):467-75. doi: 10.1007/s00418-010-0685-y. Epub 2010 Mar 17.

Abstract

Tumour angioneogenesis is associated with the reexpression of oncofetal fibronectin (oncFn) and tenascin-C (oncTn-C) splice variants, which may serve as targets for antibody-based pharmacodelivery. Knowledge of the vascular distribution and organization in different tumours is of importance for the understanding of tumour vessel formation and might be crucial for therapy. Therefore, human SIP format antibodies against Fn ED-A, Fn ED-B and Tn-C A and C splice domains were used for immunofluorescence labelling in renal, lung, oral, colon, breast and urinary bladder carcinoma specimens and in a renal carcinoma xenograft. The spatial relation to stroma, vessels and vascular basement membrane (vBM) was analysed including CD31 and laminin alpha4 chain antibodies. Renal cell carcinomas and atypical carcinoid of the lung revealed vessel-restricted oncFn and/or oncTn-C depositions; all other entities showed a variable stroma positivity including vessels. The individual pattern of oncFn/oncTn-C incorporation in the vBM depended on tumour type, vessel size and intratumoural heterogeneity. There was a stratification of the vessel wall showing luminal oncFn and extraluminal oncTn-C depositions. As shown in the xenograft, perivascular oncTn-C is provided by carcinoma cells. In conclusion, tumours differ in the pattern of Fn or Tn-C isoform positivity in the vessel wall, potentially representing a tumour type specific endothelial cell-tumour cell-stromal cell interaction. Carcinoma cells themselves are involved in vascular Tn-C matrix organization. Up to antigen distribution, Fn and Tn-C domain antibodies may serve as vehicles for antiangiogenetic and antifibrotic agents; oncFn/oncTn-C based targeting should be adapted individually.

摘要

肿瘤血管生成与癌胚纤维连接蛋白(oncFn)和 tenascin-C(oncTn-C)拼接变体的重新表达有关,这些拼接变体可能成为基于抗体的药物传递的靶点。了解不同肿瘤中的血管分布和组织对于理解肿瘤血管形成很重要,并且可能对治疗至关重要。因此,使用针对 Fn ED-A、Fn ED-B 和 Tn-C A 和 C 拼接结构域的人 SIP 格式抗体进行免疫荧光标记,用于肾、肺、口腔、结肠、乳腺和膀胱癌标本以及肾癌细胞异种移植的研究。分析了与基质、血管和血管基底膜(vBM)的空间关系,包括 CD31 和层粘连蛋白α4 链抗体。肾细胞癌和肺的非典型类癌显示血管受限的 oncFn 和/或 oncTn-C 沉积;所有其他实体均显示出可变的基质阳性,包括血管。oncFn/oncTn-C 在 vBM 中的整合模式取决于肿瘤类型、血管大小和肿瘤内异质性。血管壁存在分层,显示腔内 oncFn 和腔外 oncTn-C 沉积。如异种移植中所示,血管周围的 oncTn-C 由癌细胞提供。总之,肿瘤在血管壁中 Fn 或 Tn-C 亚型阳性的模式不同,这可能代表肿瘤类型特异性的内皮细胞-肿瘤细胞-基质细胞相互作用。癌细胞本身参与血管 Tn-C 基质组织。就抗原分布而言,Fn 和 Tn-C 结构域抗体可作为抗血管生成和抗纤维化药物的载体;oncFn/oncTn-C 为基础的靶向治疗应个体化。

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