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人黑色素瘤细胞中细胞黏附分子CD54/CD11a和CD58/CD2的差异表达及其在与细胞毒性细胞相互作用中的功能作用。

Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells.

作者信息

Altomonte M, Gloghini A, Bertola G, Gasparollo A, Carbone A, Ferrone S, Maio M

机构信息

Advanced Immunotherapeutics Unit, C. R. O., Aviano, Italy.

出版信息

Cancer Res. 1993 Jul 15;53(14):3343-8.

PMID:7686816
Abstract

Immunohistochemical staining with monoclonal antibodies showed a differential distribution of intercellular adhesion molecule 1 (ICAM-1/CD54) and lymphocyte function-associated antigen 3 (LFA-3/CD58) and their respective counterreceptors lymphocyte function-associated antigens 1 (LFA-1/CD11a) and 2 (LFA-2/CD2) on ten melanoma cell lines and in 46 surgically removed metastatic melanoma lesions. CD11a and CD2 were not detected on melanoma cells while CD54 and CD58 were coexpressed on the majority of the melanoma cell populations investigated. CD54 showed a higher degree of intra- and intertumor heterogeneity than CD58. gamma-Interferon and/or tumor necrosis factor alpha upregulated the expression of CD54 by melanoma cells, but neither modulated that of CD58 nor induced that of CD11a and CD2. Anti-CD54 and anti-CD58 monoclonal antibodies partially inhibited the lysis of melanoma cells by allogeneic natural killer cells, lymphokine-activated killer cells and, to a greater extent, by autologous tumor-infiltrating lymphocytes. Soluble CD54 (cCD54) purified from serum of patients with melanoma inhibited the lysis of melanoma cells F0-1 by natural killer cells in a dose-dependent fashion. These results suggest that membrane-bound CD54 and CD58 and cCD54 play a role in host-tumor interactions in patients with malignant melanoma and may account for the relationship between CD54 expression in primary lesions and the clinical course of disease.

摘要

用单克隆抗体进行的免疫组织化学染色显示,细胞间黏附分子1(ICAM-1/CD54)和淋巴细胞功能相关抗原3(LFA-3/CD58)及其各自的反受体淋巴细胞功能相关抗原1(LFA-1/CD11a)和2(LFA-2/CD2)在10种黑色素瘤细胞系和46个手术切除的转移性黑色素瘤病灶中分布不同。黑色素瘤细胞上未检测到CD11a和CD2,而在所研究的大多数黑色素瘤细胞群体上,CD54和CD58共表达。与CD58相比,CD54在肿瘤内和肿瘤间表现出更高程度的异质性。γ干扰素和/或肿瘤坏死因子α上调了黑色素瘤细胞CD54的表达,但既未调节CD58的表达,也未诱导CD11a和CD2的表达。抗CD54和抗CD58单克隆抗体部分抑制了同种异体自然杀伤细胞、淋巴因子激活的杀伤细胞对黑色素瘤细胞的杀伤作用,并且在更大程度上抑制了自体肿瘤浸润淋巴细胞对黑色素瘤细胞的杀伤作用。从黑色素瘤患者血清中纯化的可溶性CD54(cCD54)以剂量依赖方式抑制自然杀伤细胞对黑色素瘤细胞F0-1的杀伤作用。这些结果表明,膜结合型CD54和CD58以及cCD54在恶性黑色素瘤患者的宿主-肿瘤相互作用中发挥作用,并且可能解释了原发性病灶中CD54表达与疾病临床进程之间的关系。

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