Applied Physiology Research Center, Cardiovascular Research Institute, Isfahan University of Medical sciences, Isfahan, Iran.
Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
Arch Med Res. 2022 Jul;53(5):461-468. doi: 10.1016/j.arcmed.2022.05.003. Epub 2022 May 20.
The transmembrane receptor podoplanin (PDPN) is a platelet aggregation-inducing factor, which is widely expressed in various malignant tumors such as squamous cell carcinomas, mesotheliomas, glioblastomas. Podoplanin regulates a pathway leading to cell invasion and migration. Glioblastoma multiforme (GBM) is the most aggressive and invasive tumor of the central nervous system. A high level of PDPN expression has been reported to be associated with reduced survival, cancer aggression and migration. Aim of study to determine the effect of anti-podoplanin antibody on cell-platelet aggregation, cell invasion and viability in Uppsala 87 malignant glioma (U87MG) cell lines.
The expression of podoplanin on U87MG cells was measured using flowcytometry. The dimethyl-thiazol diphenyl-tetrazolium bromide (MTT) assay was used to measure U87MG cell proliferation after treatment by anti-podoplanin monoclonal antibody (NZ-1.3). The invasion of cancer cells was assessed by using a novel microfluidic based assay.
The results show reduction of cell viability and cell migration after treatment with anti-podoplanin antibody. After co- treatment of U87MG cells and platelets with and without anti-podoplanin antibody, the cell-platelet aggregation was significantly reduced in anti-podoplanin treated cell.
Podoplanin is involved in aggregation of gliobastoma cells, and their viability and invasion and its neutralizing antibody can inhibit this process. So, blocking of podoplanin may be representing a promising therapeutic approach to glioblastoma multiform cancer therapy.
跨膜受体 podoplanin（PDPN）是一种诱导血小板聚集的因子，广泛表达于各种恶性肿瘤，如鳞状细胞癌、间皮瘤、胶质母细胞瘤。Podoplanin 调节细胞侵袭和迁移的途径。多形性胶质母细胞瘤（GBM）是中枢神经系统最具侵袭性和侵略性的肿瘤。有报道称，PDPN 的高表达与降低的存活率、癌症侵袭性和迁移有关。本研究旨在确定抗 podoplanin 抗体对 Uppsala 87 恶性神经胶质瘤（U87MG）细胞系中细胞-血小板聚集、细胞侵袭和活力的影响。
使用流式细胞术测量 U87MG 细胞上 podoplanin 的表达。使用二甲噻唑二苯基四唑溴盐（MTT）测定抗 podoplanin 单克隆抗体（NZ-1.3）处理后 U87MG 细胞的增殖。通过新型微流控测定法评估癌细胞的侵袭。
结果表明，用抗 podoplanin 抗体处理后，细胞活力和迁移减少。在用和不用抗 podoplanin 抗体共处理 U87MG 细胞和血小板后，抗 podoplanin 处理的细胞中细胞-血小板聚集明显减少。
Podoplanin 参与胶质母细胞瘤细胞的聚集及其活力和侵袭，其中和抗体可抑制这一过程。因此，阻断 podoplanin 可能代表一种有前途的胶质母细胞瘤多形性癌症治疗方法。
