Naor David, Nedvetzki Shlomo, Golan Itshak, Melnik Lora, Faitelson Yoram
The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Crit Rev Clin Lab Sci. 2002 Nov;39(6):527-79. doi: 10.1080/10408360290795574.
CD44 is a multistructural and multifunctional cell surface molecule involved in cell proliferation, cell differentiation, cell migration, angiogenesis, presentation of cytokines, chemokines, and growth factors to the corresponding receptors, and docking of proteases at the cell membrane, as well as in signaling for cell survival. All these biological properties are essential to the physiological activities of normal cells, but they are also associated with the pathologic activities of cancer cells. Experiments in animals have shown that targeting of CD44 by antibodies, antisense,and CD44-soluble proteins markedly reduces the malignant activities of various neoplasms, stressing the therapeutic potential of anti-CD44 agents. Furthermore, because alternative splicing and posttranslational modifications generate many different CD44 sequences, including, perhaps, tumor-specific sequences, the production of anti-CD44 tumor-specific agents may be a realistic therapeutic approach. However, in many cancers (renal cancer and non-Hodgkin's lymphomas are exceptions), a high level of CD44 expression is not always associated with an unfavorable outcome. On the contrary, in some neoplams CD44 upregulation is associated with a favorable outcome. Even worse, in many cases different research grows analyzing the same neoplastic disease reached contradictory conclusions regarding the correlation between CD44 expression and disease prognosis, possibly due to differences in methodology. These problems must be resolved before applying anti-CD44 therapy to human cancers.
CD44是一种多结构、多功能的细胞表面分子，参与细胞增殖、细胞分化、细胞迁移、血管生成、细胞因子、趋化因子和生长因子向相应受体的呈递、蛋白酶在细胞膜上的对接以及细胞存活信号传导。所有这些生物学特性对正常细胞的生理活动至关重要，但它们也与癌细胞的病理活动相关。动物实验表明，用抗体、反义核酸和可溶性CD44蛋白靶向CD44可显著降低各种肿瘤的恶性活性，这突出了抗CD44药物的治疗潜力。此外，由于可变剪接和翻译后修饰产生了许多不同的CD44序列，包括可能的肿瘤特异性序列，生产抗CD44肿瘤特异性药物可能是一种切实可行的治疗方法。然而，在许多癌症中（肾癌和非霍奇金淋巴瘤除外），高水平的CD44表达并不总是与不良预后相关。相反，在一些肿瘤中，CD44上调与良好预后相关。更糟糕的是，在许多情况下，针对同一肿瘤性疾病进行分析的不同研究在CD44表达与疾病预后的相关性方面得出了相互矛盾的结论，这可能是由于方法学上的差异。在将抗CD44疗法应用于人类癌症之前，必须解决这些问题。
