Sharma Bharti, Agriantonis George, Shafaee Zahra, Twelker Kate, Bhatia Navin D, Kuschner Zachary, Arnold Monique, Agcon Aubrey, Dave Jasmine, Mestre Juan, Arora Shalini, Ghanta Hima, Whittington Jennifer
Department of Surgery, NYC Health and Hospitals, Elmhurst Hospital Center, New York, NY 11373, USA.
Department of Surgery, Icahn School of Medicine at the Mount Sinai Hospital, New York, NY 10029, USA.
Cancers (Basel). 2024 Dec 3;16(23):4051. doi: 10.3390/cancers16234051.
Glioblastoma multiforme (GBM) is a malignant primary brain tumor categorized as a Grade 4 astrocytic glioma by the World Health Organization (WHO). Some of the established risk factors of GBM include inherited genetic syndromes, body mass index, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and therapeutic ionizing radiation. Vascular anomalies, including local and peripheral thrombosis, are common features of GBM. Podoplanin (PDPN), a ligand of the C-type lectin receptor (CLEC-2), promotes platelet activation, aggregation, venous thromboembolism (VTE), lymphatic vessel formation, and tumor metastasis in GBM patients. It is regulated by Prox1 and is expressed in developing and adult mammalian brains. It was initially identified on lymphatic endothelial cells (LECs) as the E11 antigen and on fibroblastic reticular cells (FRCs) of lymphoid organs and thymic epithelial cells as gp38. In recent research studies, its expression has been linked with prognosis in GBM. PDPN-expressing cancer cells are highly pernicious, with a mutant aptitude to form stem cells. Such cells, on colocalization to the surrounding tissues, transition from epithelial to mesenchymal cells, contributing to the malignant carcinogenesis of GBM. PDPN can be used as an independent prognostic factor in GBM, and this review provides strong preclinical and clinical evidence supporting these claims.
多形性胶质母细胞瘤（GBM）是一种恶性原发性脑肿瘤，世界卫生组织（WHO）将其归类为4级星形细胞瘤。GBM的一些既定风险因素包括遗传综合征、体重指数、饮酒、使用非甾体抗炎药（NSAIDs）以及治疗性电离辐射。血管异常，包括局部和外周血栓形成，是GBM的常见特征。血小板结合蛋白（PDPN）是C型凝集素受体（CLEC-2）的配体，可促进GBM患者的血小板活化、聚集、静脉血栓栓塞（VTE）、淋巴管形成和肿瘤转移。它受Prox1调节，在发育中的和成年哺乳动物大脑中表达。它最初在淋巴管内皮细胞（LEC）上被鉴定为E11抗原，在淋巴器官的成纤维细胞网状细胞（FRC）和胸腺上皮细胞上被鉴定为gp38。在最近的研究中，其表达与GBM的预后相关。表达PDPN的癌细胞极具危害性，具有形成干细胞的突变能力。这些细胞与周围组织共定位时，会从上皮细胞转变为间充质细胞，促进GBM的恶性致癌过程。PDPN可用作GBM的独立预后因素，本综述提供了强有力的临床前和临床证据支持这些观点。
