Manten-Horst E, Danen E H, Smit L, Snoek M, Le Poole I C, Van Muijen G N, Pals S T, Ruiter D J
Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Int J Cancer. 1995 Jun 22;64(3):182-8. doi: 10.1002/ijc.2910640307.
Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT-PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non-, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (< or = 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44v10 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression.
CD44的表达，尤其是某些剪接变体的表达，在许多不同的动物和人类癌症中与肿瘤进展和转移形成有关。由于人类皮肤黑色素瘤是最具侵袭性的人类癌症之一，我们探讨了CD44异构体（CD44v）在黑素细胞肿瘤进展病变中的表达。此外，通过逆转录聚合酶链反应（RT-PCR）和荧光激活细胞分选（FACS）分析，我们评估了从人包皮分离的培养黑素细胞以及一组2种非转移性、2种散发性和2种高转移性人类黑色素瘤细胞系中CD44v RNA种类和CD44v的细胞表面表达。我们观察到，所有检查的黑素细胞病变均显示标准CD44（CD44s）表位的强烈均匀表达。我们在黑素细胞病变中未检测到CD44v6表达。然而，含有v5或v10的CD44异构体存在差异表达。V5分别在16%、0%、20%、67%和58%的普通痣、非典型痣、早期原发性黑色素瘤（≤1.5 mm）、晚期原发性黑色素瘤（>1.5 mm）和转移灶中表达，因此与肿瘤进展相关。相比之下，CD44v10在所有普通痣中表达，而非典型痣的一部分以及大多数原发性黑色素瘤和转移灶缺乏v10。CD44v RNA模式在培养的黑素细胞和所有黑色素瘤细胞系中非常相似。黑素细胞表达高水平的CD44s但不表达CD44v，而所有黑色素瘤细胞系在表面表达CD44v。有趣的是，v5的表达在高转移性细胞系中强烈增加。我们的结果表明CD44变异域，尤其是v5和v10，在人类黑素细胞肿瘤进展中起作用。
