CD98 at the crossroads of adaptive immunity and cancer
CD98 at the crossroads of adaptive immunity and cancer
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DOI：
10.1242/jcs.096040
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发表时间：
2012-03-15
影响因子：
4
通讯作者：
Ginsberg, Mark H.
中科院分区：
文献类型：
--
作者：
Cantor, Joseph M.;Ginsberg, Mark H.
获得性免疫是脊椎动物的一种专门化，它在保存代谢资源的同时，为无脊椎动物存在的基本先天免疫反应增加了记忆力和精致的特异性。在获得性免疫中，抗原挑战要求罕见的抗原特异性淋巴细胞极快地增殖，以产生大量克隆性扩大的效应者群体，以中和病原体。快速增殖和由此产生的克隆扩张依赖于CD98，一种其保守的同源物似乎仅限于脊椎动物的蛋白质。因此，CD98支持淋巴细胞克隆性扩增，以实现保护性适应性免疫，这一优势可以解释CD98在脊椎动物中的存在。CD98通过放大整合素信号来支持淋巴细胞克隆性扩增，整合素信号可以促进细胞增殖和防止细胞凋亡。这些整合素依赖的信号还可以刺激肿瘤的发展和侵袭、锚定独立和肿瘤细胞的快速增殖。CD98在多种肿瘤组织中高度表达，在实验性肿瘤模型中起重要作用。值得注意的是，脊椎动物拥有高度保守的CD98蛋白、CD98结合整合素和适应性免疫，也显示出侵袭性和转移性肿瘤的倾向。本文就CD98在淋巴细胞生物学和癌症中的作用作一综述。我们认为，CD98扩增的整合素信号在适应性免疫中为脊椎动物提供了生存益处，而脊椎动物反过来承担了增加癌症易感性的代价。
Adaptive immunity, a vertebrate specialization, adds memory and exquisite specificity to the basic innate immune responses present in invertebrates while conserving metabolic resources. In adaptive immunity, antigenic challenge requires extremely rapid proliferation of rare antigen-specific lymphocytes to produce large, clonally expanded effector populations that neutralize pathogens. Rapid proliferation and resulting clonal expansion are dependent on CD98, a protein whose well-conserved orthologs appear restricted to vertebrates. Thus, CD98 supports lymphocyte clonal expansion to enable protective adaptive immunity, an advantage that could account for the presence of CD98 in vertebrates. CD98 supports lymphocyte clonal expansion by amplifying integrin signals that enable proliferation and prevent apoptosis. These integrin-dependent signals can also provoke cancer development and invasion, anchorage-independence and the rapid proliferation of tumor cells. CD98 is highly expressed in many cancers and contributes to formation of tumors in experimental models. Strikingly, vertebrates, which possess highly conserved CD98 proteins, CD98-binding integrins and adaptive immunity, also display propensity towards invasive and metastatic tumors. In this Commentary, we review the roles of CD98 in lymphocyte biology and cancer. We suggest that the CD98 amplification of integrin signaling in adaptive immunity provides survival benefits to vertebrates, which, in turn, bear the price of increased susceptibility to cancer.