【作者】 左云飞；

【导师】 张嘉宁；

【作者基本信息】 大连医科大学 ， 生物化学与分子生物学， 2006， 博士

【摘要】 选择蛋白包括三种细胞粘附分子：L、E、P-选择蛋白。L-选择蛋白(L-selectin(CD62L))是淋巴细胞归巢受体，它在中性粒细胞、单核细胞、血液T淋巴细胞、B淋巴细胞、自然杀伤细胞和肿瘤细胞膜表达，主要介导白细胞与血管内皮细胞黏附。L-选择蛋白介导的粘附可能是通过L-选择蛋白配体的正调控所起作用。细胞活化后可导致L-选择蛋白从接近细胞膜的位点开始蛋白水解，这个断裂位置在Lys321-Ser322之间。L-选择蛋白水解脱落后在细胞表面留下一个6kD的跨膜断裂片段。推测L-选择蛋白的水解脱落有利于白细胞从内皮细胞上脱落和迁移穿过内皮细胞层。L-选择蛋白定位在细胞表面微绒毛的顶端，微绒毛上的粘附受体的存在有利于白细胞和血管之间的初始相互作用。三种选择蛋白的天然配体几乎都是糖蛋白、糖脂或蛋白聚糖的唾液酸化、岩藻糖基化或硫酸化的聚糖，L-选择蛋白配体作用的糖蛋白包括CD34、sgp200、endomucin和GlyCAM-1。 L-选择蛋白的正常功能是作为淋巴细胞到达外周淋巴结的归巢受体，故学者们探讨了L-选择蛋白在恶性白血病、淋巴瘤细胞中是否参与了向远距离淋巴结转移的过程。研究表明在淋巴白血病肿瘤细胞上L-选择蛋白的表达与淋巴结疾病的发生一般是平行的，L-选择蛋白在鼠淋巴瘤转移至淋巴结的过程中起促进作用。定位在外周淋巴结的人非何杰金氏淋巴瘤为L-选择蛋白阳性。Qian等使用了致癌的转基因鼠模型直接注射肿瘤细胞发现只有携带L-选择蛋白的肿瘤细胞才可能在外周淋巴结检测到。Borsig等发现内源性表达于白细胞的L-选择蛋白能够在体内影响肿瘤细胞的转移行为。Belanger等使用基因敲除小鼠观察到L-选择蛋白在T-淋巴瘤细胞形成中的作用发现L-选择蛋白在T-淋巴瘤细胞归巢后发挥其功能，L-选择蛋白参与T-淋巴瘤细胞的淋巴道转移，但L-选择蛋白的缺失不影响T-淋巴瘤细胞淋巴道转移速度。研究结果表明正常的淋巴细胞归巢机制对于肿瘤的转移可能是起作用的。然而，这些结论亦被学者们的研究所质疑。有研更多还原

【Abstract】 L-, P-, and E-selectins comprise a family of carbohydrate-binding adhesion molecules expressed by leukocytes and platelets and vascular endothelium. L-selectin (CD62L) is a lymphocyte homing receptor, which constitutively expressed on all neutrophils and monocytes, on subsets of blood borne T cells, B cells, natural killer (NK) cells and tumor cells. The ligands of L-selectin include CD34, sgp200, endomucin and GlyCAM-1. They not only reside in leukocyte, but also in many type tumor cells, which participate tumor metastasis.It has been demonstrated that solid tumor occurred in regional lymphaden disseminateion. The normal function of L-selectin is homing receptor, and L-selectin can facilitate metastasis to lymph nodes in a transgenic mouse model of carcinogenesis. Lack of L-selectin expression in the host significantly delayed the dissemination of lymphomas to peripheral tissues. This resistance of L-selectin-deficient mice to lymphoma metastasis was dependent on the intrinsic properties of lymphoma cells. This work provided definitive evidence that L-selectin play a significant role at different steps of T cell lymphoma development. But, this idea has been challenged by studies that have shown a lack of correlation between the expressions of L-selectin with the metastatic potential of lymphoma cells. Nevertheless, the way that L-selectin function in vivo and in vitro is not fully understood and numerous questions remain unanswered concerning the physiology and function. Therefore, it is conceivable that any tumor cell could randomly activate expression of L-selectin during tumor progression, and it is worth exploring a potential role of L-selectin in LN metastases of lymphoid tumors.更多还原