Seiter S, Schadendorf D, Herrmann K, Schneider M, Rösel M, Arch R, Tilgen W, Zöller M
Department of Dermatology, University Hospital, Hospitalstrasse 3, 69120 Heidelberg, Germany.
Clin Cancer Res. 1996 Mar;2(3):447-56.
In a variety of human tumors, expression of splice variants of the adhesion molecule CD44 (CD44v) has been described as correlating with tumor progression. Here, we report on the expression of CD44v in melanocytes, nevi, primary melanomas, and cutaneous and lymph node metastases. Thirteen nevi, 65 primary melanomas of varying thickness, 39 cutaneous and 15 lymph node metastases, and melanocytes and a panel of melanoma lines were tested for surface expression of the standard form of CD44 and the variant exons v5, v6, v7, v7-v8, and v10 by immunohistology or fluorescence-activated cell sorting. Melanocytes did not express any variant isoform of CD44. However, nevi, as well as primary melanoma and melanoma metastases, stained to a varying degree with anti-CD44v5, anti-CD44v7-v8, and anti-CD44v10. Exons v6 and v7 were not detected on any of these tissue specimens. Compared with nevi, expression of exon v10 was up-regulated in thick primary tumors and skin metastases. Lymph node metastases displayed elevated levels of exon v5. Expression of CD44v in melanoma lines (n = 20) differed, inasmuch as many lines did not express variant isoforms; in particular, exon v10. Interestingly, however, the few CD44v5-positive melanoma lines metastasized in the nu/nu mouse. Because benign as well as malignant growth of melanocytes was accompanied by expression of CD44 variant isoforms, a linkage between expression of CD44 variant isoforms and malignant transformation or tumor progression was excluded. Considering the function of distinct isoforms, one might speculate that expression of exon CD44v5, which was up-regulated in lymph node metastases compared with nevi and primary melanoma, provided a growth stimulus. Exon v10 is present at high density in epidermal cells. The de novo expression of this exon in nevi and the increased expression in thick melanoma and skin metastases would be in line with the assumption of an anchoring advantage in the surrounding epidermal tissue.
在多种人类肿瘤中，黏附分子CD44剪接变体（CD44v）的表达被描述为与肿瘤进展相关。在此，我们报告CD44v在黑素细胞、痣、原发性黑色素瘤以及皮肤和淋巴结转移灶中的表达情况。通过免疫组织化学或荧光激活细胞分选，对13个痣、65个不同厚度的原发性黑色素瘤、39个皮肤转移灶和15个淋巴结转移灶以及黑素细胞和一组黑色素瘤细胞系进行检测，以确定CD44标准形式以及变异外显子v5、v6、v7、v7 - v8和v10的表面表达情况。黑素细胞不表达任何CD44变异同工型。然而，痣以及原发性黑色素瘤和黑色素瘤转移灶用抗CD44v5、抗CD44v7 - v8和抗CD44v10染色呈不同程度阳性。在这些组织标本中均未检测到外显子v6和v7。与痣相比，外显子v10在厚的原发性肿瘤和皮肤转移灶中表达上调。淋巴结转移灶中外显子v5水平升高。黑色素瘤细胞系（n = 20）中CD44v的表达有所不同，因为许多细胞系不表达变异同工型；特别是外显子v10。然而，有趣的是，少数CD44v5阳性黑色素瘤细胞系在裸鼠中发生转移。由于黑素细胞的良性和恶性生长均伴有CD44变异同工型的表达，因此排除了CD44变异同工型表达与恶性转化或肿瘤进展之间的联系。考虑到不同同工型的功能，有人可能推测，与痣和原发性黑色素瘤相比，在淋巴结转移灶中上调的外显子CD44v5的表达提供了生长刺激。外显子v10在表皮细胞中高密度存在。该外显子在痣中的从头表达以及在厚的黑色素瘤和皮肤转移灶中的表达增加，符合其在周围表皮组织中具有锚定优势的假设。
