Rösel M, Seiter S, Zöller M
Department of Tumour Progression and Immune Defence, German Cancer Research Centre, Heidelberg, Germany.
J Cell Physiol. 1997 Jun;171(3):305-17. doi: 10.1002/(SICI)1097-4652(199706)171:3<305::AID-JCP9>3.0.CO;2-S.
We have described recently that expression of CD44 exon v10 (CD44v10) is down-regulated upon metastasis of squamous cell carcinoma, whereas it is up-regulated in skin metastases of malignant melanoma. The striking regulation of CD44v10 prompted us to generate a murine CD44v10-specific monoclonal antibody to define expression and possible functions of this particular CD44 variant isoform. In the mouse, expression of exon v10 was restricted to basal layers of the epidermis and squamous epithelium of the oral cavity, the esophagus, the omasum, glandular epithelium of the submandibular and the uterine gland, as well as subpopulations of bone marrow cells and activated lymphocytes. Expression started late during development, e.g., was not observed before day 16 of gestation and there was no evidence for developmental regulation of CD44v10 expression. Functional in vivo studies revealed that anti-CD44v10 had no effect on wound healing but inhibited edema and granuloma formation in delayed type hypersensitivity (DTH). Furthermore, lymphocyte-monocyte interactions could be inhibited by anti-CD44v10. Because a CD44v10 transfected tumour line did not show any distinct pattern of cell-matrix or cell-cell adhesion, the data point toward an involvement of CD44v10 in cell migration, possibly by acting as a target structure for cytokines/chemokines provided by the contacted partner cell.
我们最近报道,在鳞状细胞癌发生转移时,CD44外显子v10(CD44v10)的表达下调,而在恶性黑色素瘤的皮肤转移灶中其表达上调。CD44v10这种显著的调控促使我们制备一种鼠源CD44v10特异性单克隆抗体,以确定这种特定CD44变异体亚型的表达及可能的功能。在小鼠中,外显子v10的表达局限于表皮的基底层、口腔、食管、重瓣胃的鳞状上皮、下颌下腺和子宫腺的腺上皮,以及骨髓细胞亚群和活化淋巴细胞。表达在发育后期开始,例如在妊娠第16天之前未观察到,且没有证据表明CD44v10表达存在发育调控。体内功能研究表明,抗CD44v10对伤口愈合没有影响,但在迟发型超敏反应(DTH)中可抑制水肿和肉芽肿形成。此外,抗CD44v10可抑制淋巴细胞 - 单核细胞相互作用。由于转染了CD44v10的肿瘤细胞系未显示出任何明显的细胞 - 基质或细胞 - 细胞黏附模式,这些数据表明CD44v10可能参与细胞迁移,可能是通过充当接触的伙伴细胞提供的细胞因子/趋化因子的靶结构来实现的。