Hsu P L, Hsu S M
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, USA.
Cancer Res. 1998 Dec 1;58(23):5507-13.
Heat shock proteins (HSPs) or stress proteins are synthesized by cells in response to environmental stress. Expression of HSPs by cells may have important physiological or pathological implications. In this study, we carried out an immunohistochemical and biochemical examination of low (hsp27), intermediate (hsp60), and high (hsp89) molecular weight HSP expression in reactive lymph nodes and in lymph nodes of patients with various types of lymphomas. In normal or reactive lymphoid tissues, hsp89 is abundant in large "transformed" lymphoid cells and immunoblasts. Hsp60 is widely distributed in lymphoid tissues, whereas hsp27 is absent in all lymphoid cells and histiocytes. Among lymphomas, the Hodgkin's Reed-Sternberg (H-RS) cells in Hodgkin's disease (HD) had the greatest abundance of hsp89 and hsp60 and, in 20% of cases, hsp27, in contrast to a much weaker staining of anti-hsp89 and -hsp60 in the background reactive lymphoid cells. The large lymphoid cells in small lymphocytic lymphoma are also rich in hsp89, but not hsp60 and hsp27. In contrast, the malignant cells in anaplastic large cell lymphoma and most high-grade tumors, including immunoblastic lymphomas, expressed minimal amounts of hsp89 and hsp60 and virtually no hsp27. Thus, the cellular level of HSPs was neither correlated with the proliferative capacity nor with the aggressiveness of the lymphomas. Hsp89, hsp60, and hsp27, as well, serve critical roles in the chaperoning of cellular proteins (e.g., a Mr 43,000 protein) in H-RS cells. The known interactions of HSPs with Rb, p53, peptide-MHC class II complexes, and cofactors of the glucocorticoid hormone receptor have further broadened the importance of HSPs in cell metabolism and in response to extracellular signals for proliferation, differentiation, or growth suppression (or apoptosis) of H-RS cells. Abundant HSP expression is seen only in HD, but not in other lymphomas. Such expression could have vital roles in the pathogenesis of HD.
热休克蛋白（HSPs）或应激蛋白是细胞在应对环境应激时合成的。细胞中HSPs的表达可能具有重要的生理或病理意义。在本研究中，我们对反应性淋巴结以及各类淋巴瘤患者的淋巴结进行了免疫组织化学和生化检测，以检测低分子量（hsp27）、中等分子量（hsp60）和高分子量（hsp89）热休克蛋白的表达情况。在正常或反应性淋巴组织中，hsp89在大型“转化”淋巴细胞和免疫母细胞中含量丰富。hsp60广泛分布于淋巴组织中，而hsp27在所有淋巴细胞和组织细胞中均不存在。在淋巴瘤中，霍奇金病（HD）中的霍奇金-里德-斯腾伯格（H-RS）细胞中hsp89和hsp60含量最为丰富，20%的病例中存在hsp27，相比之下，背景反应性淋巴细胞中抗hsp89和 -hsp60的染色要弱得多。小淋巴细胞淋巴瘤中的大型淋巴细胞也富含hsp89，但不含有hsp60和hsp27。相反，间变性大细胞淋巴瘤和大多数高级别肿瘤（包括免疫母细胞淋巴瘤）中的恶性细胞表达的hsp89和hsp60极少，几乎不表达hsp27。因此，热休克蛋白的细胞水平与淋巴瘤的增殖能力和侵袭性均无关联。hsp89、hsp60以及hsp27在H-RS细胞中对细胞蛋白（如分子量为43,000的蛋白）的伴侣作用中也发挥着关键作用。热休克蛋白与Rb、p53、肽-主要组织相容性复合体II类复合物以及糖皮质激素受体辅助因子之间已知的相互作用，进一步拓展了热休克蛋白在细胞代谢以及H-RS细胞对细胞外增殖、分化或生长抑制（或凋亡）信号反应中的重要性。仅在霍奇金病中可见热休克蛋白的丰富表达，而在其他淋巴瘤中则未见到。这种表达可能在霍奇金病的发病机制中发挥重要作用。
