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

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。

Podoplanin, originally found on the surface of podocytes, belongs to the family of type-1 transmembrane sialomucin-like glycoproteins. Podoplanin is expressed on the surface of the lymphatic endothelium cell （LEC） and some normal 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 also expressed on the surface of malignant tumor cells, such as most squamous cell carcinomas, germ cell tumors, and tumors 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 metastasis. Podoplanin is useful in determining the degree of malignancy, metastasis and prognosis, and may provide a new approach for anti-tumor therapy.