Lefranc Florence, Mathieu Véronique, Kiss Robert
Florence Lefranc, Véronique Mathieu, Robert Kiss, Laboratory of Toxicology, Faculty of Pharmacy, Université Libre de Bruxelles, Brussels 1050, Belgium.
World J Biol Chem. 2011 Sep 26;2(9):193-201. doi: 10.4331/wjbc.v2.i9.193.
Gliomas and melanomas are associated with dismal prognosis because of their marked intrinsic resistance to proapoptotic stimuli, such as conventional chemotherapy and radiotherapy, as well as their ability to escape immune cell attacks. In addition, gliomas and melanomas display pronounced neoangiogenesis. Galectin-1 is a hypoxia-sensitive protein, which is abundantly secreted by glioma and melanoma cells, which displays marked proangiogenic effects. It also provides immune tolerogenic environments to melanoma and glioma cells through the killing of activated T cells that attack these tumor cells. Galectin-1 protects glioma and melanoma cells against cytotoxic insults (including chemotherapy and radiotherapy) through a direct role in the unfolded protein response. Altogether, these facts clearly point to galectin-1 as an important target to be combated in gliomas and melanomas in order to: (1) weaken the defenses of these two types of cancers against radiotherapy, chemotherapy and immunotherapy/vaccine therapy; and (2) reinforce antiangiogenic therapies. In the present article, we review the biochemical and molecular biology-related pathways controlled by galectin-1, which are actually beneficial for melanoma and glioma cells, and therefore detrimental for melanoma and glioma patients.
胶质瘤和黑色素瘤的预后较差,这是因为它们对促凋亡刺激(如传统化疗和放疗)具有显著的内在抗性,并且能够逃避免疫细胞的攻击。此外,胶质瘤和黑色素瘤表现出明显的新生血管形成。半乳凝素-1是一种对缺氧敏感的蛋白质,由胶质瘤和黑色素瘤细胞大量分泌,具有显著的促血管生成作用。它还通过杀死攻击这些肿瘤细胞的活化T细胞,为黑色素瘤和胶质瘤细胞提供免疫耐受环境。半乳凝素-1通过在未折叠蛋白反应中直接发挥作用,保护胶质瘤和黑色素瘤细胞免受细胞毒性损伤(包括化疗和放疗)。总之,这些事实清楚地表明,半乳凝素-1是胶质瘤和黑色素瘤治疗中一个重要的靶点,目的是:(1)削弱这两种癌症对放疗、化疗和免疫治疗/疫苗治疗的防御能力;(2)加强抗血管生成治疗。在本文中,我们综述了由半乳凝素-1控制的与生物化学和分子生物学相关的途径,这些途径实际上对黑色素瘤和胶质瘤细胞有益,因此对黑色素瘤和胶质瘤患者有害。