Podoplanin促进肿瘤侵袭转移的机制及其临床意义

Mechanisms of Tumor Invasion and Metastasis Induced by Podoplanin and Its Clinical Implication

  • 摘要: Podoplanin 最早发现于肾小球的足突细胞膜,属于Ⅰ型黏液样跨膜糖蛋白。Podoplanin 表达于淋巴管内皮细胞(LEC )和部分正常组织细胞的表面,在促进淋巴管生成、防止细胞粘附和维持肾小球足突细胞形态方面具有重要作用。作为LEC 的特异性标记物,许多研究通过检测Podoplanin 在LEC 上的表达,测量肿瘤内部和周边的微淋巴管密度(LMVD),进而阐明LMVD 和肿瘤淋巴结转移、肿瘤预后的相关性。Podoplanin 还广泛表达于恶性肿瘤细胞的表面,如大多数的鳞状细胞癌、生殖细胞肿瘤和中枢神经系统肿瘤。Podoplanin 可以促使ERM蛋白磷酸化,调整Rho 家族成员GTP 酶的活性和重组肌动蛋白细胞骨架等,最终引起细胞的侵袭和转移。因此,Podoplanin 在判断肿瘤的恶性程度、转移及预后方面具有重要意义,并有望为抗肿瘤治疗提供一条新思路。

     

    Abstract: Podoplanin, originally found on the surface of podocytes, belongs to the family of type-1 transmembrane si-alomucin-like glycoproteins. Podoplanin is expressed on the surface of the lymphatic endothelium cell (LEC) and some nor-mal tissues. It is involved in lymphatic vessel (LV) formation and the regulation of the shape of the podocyte foot and plays an important role in preventing cellular adhesion. As a specific marker of LEC, podoplanin has been used in many studies to detect LEC and to evaluate the LV microvascular density (LVMD) in peritumoral and intratumoral areas. Podoplanin is al -so expressed on the surface of malignant tumor cells, such as most squamous cell carcinomas, germ cell tumors, and tu-mors of the central nervous system. Podoplanin can increase the phosphorylation of ERM proteins, modulate the activity of Rho-family GTPases (in particular RhoA) and remodel the actin cytoskeleton, thus can induce tumor invasion and metasta-sis. Podoplanin is useful in determining the degree of malignancy, metastasis and prognosis, and may provide a new ap-proach for anti-tumor therapy.

     

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