Expression of Epstein-Barr virus latent membrane proteins leads to changes in keratinocyte cell adhesion
Expression of Epstein-Barr virus latent membrane proteins leads to changes in keratinocyte cell adhesion
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DOI：
10.1177/000348949910800906
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发表时间：
1999-09-01
影响因子：
1.4
通讯作者：
Coltrera, MD
中科院分区：
文献类型：
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作者：
Farwell, DG;McDougall, JK;Coltrera, MD
Epstein-Barr 病毒 (EBV) 具有 3 种潜在膜蛋白 (LMP) - LMP1、LMP2a 和 LMP2b - 在鼻咽癌中表达。使用表达 LMP2a 和 LMP2b 以及共表达 LMP1/LMP2a 的角质形成细胞系，我们培养了器官型筏培养物，以分析细胞粘附分子 ICAM-1 的形态和表达的变化； α2、α3、α5、β1和α6β4整联蛋白；层粘连蛋白5; E-钙粘蛋白；和桥粒斑蛋白。与亲代细胞系相比，表达 LMP2a 或 LMP2b 的细胞在成熟和通过正常鳞状分层进展的能力方面存在缺陷。共表达 LMP1/LMP2a 的细胞还表现出对真皮筏等效物的“假入侵”。在表达 LMP 的细胞系中，层粘连蛋白 5 和 α 6 β 4 和 β 1 整合素的基底上表达出现一致且显着的上调。 ICAM-1 在对照细胞系中不表达，但在表达 LMP 的细胞系中表达上调。在表达 LMP 的细胞系中，α 3 和 α 5 整合素的表达也上调，而 α 2 则表现出正常基底层表达的丧失。 E-钙粘蛋白和桥粒斑蛋白的表达模式基本没有变化。我们得出结论，LMP2a 和 LMP2b 单独表达以及 LMP1/LMP2a 共表达能够改变角质形成细胞粘附分子的表达，与鼻咽癌一致。
Epstein-Barr virus (EBV) has 3 latent membrane proteins (LMPs)- LMP1, LMP2a, and LMP2b - which are expressed in nasopharyngeal carcinoma. Using keratinocyte cell lines expressing LMP2a and LMP2b and coexpressing LMP1/LMP2a, we grew organotypic raft cultures to analyze changes in morphology and expression of the cell adhesion molecule ICAM-1; alpha 2, alpha 3, alpha 5, beta 1, and alpha 6 beta 4 integrins; laminin 5; E-cadherin; and desmoplakin. Cells expressing LMP2a or LMP2b were defective in their ability to mature and progress through normal squamous stratification when compared to the parental cell lines. Cells coexpressing LMP1/LMP2a additionally demonstrated "pseudoinvasion" into the raft dermal equivalent. There was a consistent and dramatic up-regulation in the suprabasal expression of laminin 5 and alpha 6 beta 4 and beta 1 integrins in the LMP-expressing cell lines. ICAM-1, not expressed in the control cell lines, was up-regulated in the LMP-expressing cell lines. Expression of alpha 3 and alpha 5 integrins was also up-regulated in the LMP-expressing cell lines, while alpha 2 demonstrated a loss of the normal basal layer expression. E-cadherin and desmoplakin expression patterns were essentially unchanged. We conclude that LMP2a and LMP2b singly, and LMP1/LMP2a coexpressed, are capable of altering keratinocyte cell adhesion molecule expression consistent with nasopharyngeal carcinoma.