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与转移性肿瘤细胞相关的细胞表面糖蛋白CD44的剪接变体在人类和食蟹猴的正常组织中表达。

Splice variants of the cell surface glycoprotein CD44 associated with metastatic tumour cells are expressed in normal tissues of humans and cynomolgus monkeys.

作者信息

Heider K H, Mulder J W, Ostermann E, Susani S, Patzelt E, Pals S T, Adolf G R

机构信息

Boehringer Ingelheim Research and Development, Vienna, Austria.

出版信息

Eur J Cancer. 1995 Dec;31A(13-14):2385-91. doi: 10.1016/0959-8049(95)00420-3.

Abstract

Certain isoforms of the CD44 glycoprotein family play an essential role in the metastatic spread of tumour cells. Protein expression of such CD44 isoforms has also been observed in a variety of human malignancies. In this study, we compared the expression of exon v5- and v6-containing CD44 isoforms in normal human and cynomolgus monkey (Macacca fasciculata) tissues. Cloning and sequencing of cynomolgus CD44 exons v5 and v6 revealed a homology of 97% and 95%, respectively, between man and monkey. Two monoclonal antibodies (MAbs) directed against an epitope encoded by human exon v5 (VFF8) and an epitope encoded by exon v6 (VFF18) were used to determine expression of CD44 isoforms in man and monkey. Immunohistochemical screening of a representative profile of normal human and cynomolgus tissues revealed that expression of exon v5- and v6-containing CD44 isoforms was almost identical in the two species. Exon v6 staining was observed only in a subset of epithelial tissues, whereas v5 staining was additionally detected on certain non-epithelial tissues. These data suggest that cynomolgus monkey could serve as a system to test the usefulness of antivariant CD44 MAbs with regard to antibody-based tumour therapy.

摘要

CD44糖蛋白家族的某些亚型在肿瘤细胞的转移扩散中起着至关重要的作用。在多种人类恶性肿瘤中也观察到了此类CD44亚型的蛋白表达。在本研究中,我们比较了正常人组织和食蟹猴(食蟹猕猴)组织中含外显子v5和v6的CD44亚型的表达情况。对食蟹猴CD44外显子v5和v6进行克隆和测序后发现,人与猴之间的同源性分别为97%和95%。使用两种针对人类外显子v5编码的表位(VFF8)和外显子v6编码的表位(VFF18)的单克隆抗体(MAb)来确定人和猴中CD44亚型的表达。对一组具有代表性的正常人和食蟹猴组织进行免疫组织化学筛查后发现,含外显子v5和v6的CD44亚型在这两个物种中的表达几乎相同。仅在上皮组织的一个子集中观察到外显子v6染色,而在某些非上皮组织上还检测到了v5染色。这些数据表明,食蟹猴可作为一个系统,用于测试抗变异型CD44单克隆抗体在基于抗体的肿瘤治疗方面的有效性。

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