Duncan L M, Bouffard D, Howard C, Mihm M C, Byers H R
Dermatopathology Unit, Massachusetts General Hospital, Boston 02114-2698, USA.
Mod Pathol. 1996 Sep;9(9):938-43.
Integrin alpha 2 beta 1 is a transmembrane protein receptor for collagen and laminin previously reported as a melanoma tumor progression antigen. alpha-Actinin is an actin-binding protein reported to interact with the cytoplasmic domain of the beta 1-integrin chain of alpha 2 beta 1. In vitro, both alpha 2 beta 1 and alpha-actinin play a role in melanoma cell motility. In turn, increased melanoma cell line motility (measured as mean migration rates), correlates with metastasis. To determine the in situ distribution of these proteins, we used monoclonal antibodies directed against the alpha 2-integrin subunit of alpha 2 beta 1 and alpha-actinin on frozen sections of 33 melanocytic proliferations, which included dermal nevi, primary melanomas, and metastatic melanomas. We found that the superficial portion of all of the melanocytic proliferations tested stained for alpha-actinin. In benign nevi and superficial spreading melanoma, there was a notable loss of staining for alpha-actinin in the cells in the deep reticular dermis. In contrast, alpha-actinin was present on almost all of the tumor cells in the nodular melanomas and the melanoma metastases. Tumors stained either uniformly positive or uniformly negative for alpha 2 beta 1; the expression of this protein correlated with the later stages of melanoma progression. Our findings suggest that alpha-actinin protein levels initially decrease and then increase during melanocytic tumor progression, whereas the alpha 2 subunit protein appears in the later stages of melanoma progression. The variable distribution of these proteins is evidence for the differential adhesive and motile properties of subpopulations of cells in melanocytic proliferations.
整合素α2β1是一种针对胶原蛋白和层粘连蛋白的跨膜蛋白受体，此前被报道为黑色素瘤肿瘤进展抗原。α-辅肌动蛋白是一种肌动蛋白结合蛋白，据报道可与α2β1的β1整合素链的细胞质结构域相互作用。在体外，α2β1和α-辅肌动蛋白均在黑色素瘤细胞运动中发挥作用。反过来，黑色素瘤细胞系运动性增加（以平均迁移率衡量）与转移相关。为了确定这些蛋白质的原位分布，我们使用针对α2β1的α2整合素亚基和α-辅肌动蛋白的单克隆抗体，对33个黑素细胞增殖样本的冰冻切片进行检测，这些样本包括皮肤痣、原发性黑色素瘤和转移性黑色素瘤。我们发现，所有检测的黑素细胞增殖样本的浅表部分均有α-辅肌动蛋白染色。在良性痣和浅表扩散性黑色素瘤中，深部网状真皮层的细胞中α-辅肌动蛋白染色明显缺失。相比之下，结节性黑色素瘤和黑色素瘤转移灶中的几乎所有肿瘤细胞均有α-辅肌动蛋白。肿瘤的α2β1染色要么均匀阳性，要么均匀阴性；该蛋白的表达与黑色素瘤进展的后期阶段相关。我们的研究结果表明，在黑素细胞肿瘤进展过程中，α-辅肌动蛋白水平最初下降，然后上升，而α2亚基蛋白出现在黑色素瘤进展的后期阶段。这些蛋白质的可变分布证明了黑素细胞增殖中细胞亚群具有不同的黏附性和运动性。
