Department of Pathology, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Histol Histopathol. 2013 Mar;28(3):293-9. doi: 10.14670/HH-28.293.
Podoplanin, a type-1 transmembrane glycoprotein, was originally named due to its expression in renal podocytes of rats. It was subsequently detected in a variety of normal human tissues, including lymphatic endothelium. Although podoplanin has been identified as the endogenous ligand of C-type lectin-like receptor 2 (CLEC-2) on platelets, its physiological functions and pathways remain largely unknown. A role in lymphangiogenesis has been suggested, since podoplanin-deficient mice were found to die at birth with a phenotype of dilated, malfunctioning lymphatic vessels and lymphedema. Podoplanin is invariably expressed in some tumors, such as lymphangioma, seminoma and follicular dendritic cell tumor, but tumor cell expression of podoplanin is highly variable in squamous cell carcinoma (SCC). It has been found that high podoplanin expression is associated with lymph node metastasis and poor prognosis in SCC of the upper aerodigestive tract. Now there is growing evidence that podoplanin is also involved in carcinogenesis, cell motility, tumor invasiveness, platelet aggregation and hematogenous metastasis. Additionally, animal studies confirmed some in vivo effects of podoplanin-overexpressing tumors, including formation of more tumor lymphatic vessels, larger lymph node metastases, more platelet aggregation, and more pulmonary metastases. Several recently developed anti-podoplanin antibodies, such as NZ-1, P2-0 and hP2-0, have been shown to attenuate podoplanin-induced platelet aggregation and prevent experimental hematogenous metastasis in nude mice. These antibodies may be applied in preclinical and clinical studies to evaluate the possibility of podoplanin-targeted therapy.
足突蛋白（Podoplanin）是一种Ⅰ型跨膜糖蛋白，最初因其在大鼠肾足细胞中的表达而得名。随后，在多种正常人体组织中也检测到了它的存在，包括淋巴内皮细胞。虽然足突蛋白已被确定为血小板上 C 型凝集素样受体 2（CLEC-2）的内源性配体，但它的生理功能和途径仍知之甚少。有人提出它在淋巴管生成中发挥作用，因为发现缺乏足突蛋白的小鼠在出生时就会死亡，其淋巴管扩张、功能失调，并伴有淋巴水肿。在一些肿瘤中，如淋巴管瘤、精原细胞瘤和滤泡树突状细胞瘤，总是会表达足突蛋白，但在鳞状细胞癌（SCC）中，肿瘤细胞对足突蛋白的表达则高度可变。已经发现，高表达足突蛋白与 SCC 在上呼吸道的淋巴结转移和预后不良有关。现在越来越多的证据表明，足突蛋白也参与了致癌作用、细胞迁移、肿瘤侵袭性、血小板聚集和血行转移。此外，动物研究证实了过表达足突蛋白的肿瘤的一些体内效应，包括形成更多的肿瘤淋巴管、更大的淋巴结转移、更多的血小板聚集和更多的肺转移。几种最近开发的抗足突蛋白抗体，如 NZ-1、P2-0 和 hP2-0，已被证明可以减弱足突蛋白诱导的血小板聚集，并防止裸鼠实验性血行转移。这些抗体可能在临床前和临床研究中应用，以评估针对足突蛋白的治疗的可能性。
