Recognition of the Sodium-Dependent Phosphate Transporter NaPi2b by Monoclonal Antibodies N-NaPi2b in Ovarian Cancer Cells

L. Minigulova, V. Skripova, A. K. Nurgalieva, D. Savenkova, A. S. Kozlova, N. Akberova, D. Reshetnikova, L. Savinska, O. Garifulin, M. Bogdanov, R. Kiyamova
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Abstract

The sodium-dependent phosphate cotransporter NaPi2b encoded by the SLC34A2 gene is a trans-membrane protein that belongs to the family of phosphate transporters SLC34 and is involved in main-taining phosphate homeostasis in the human body. The phosphate transporter NaPi2b is expressed in several normal tissues and body organs, as well as in malignant neoplasms of the ovary, lung, colorectal, and other types of cancer. The membrane protein NaPi2b is a target for therapeutic humanized antibodies Rebmab200, XMT-1535, and XMT-1536 in cancer cells. These antibodies were created based on MX35 antibodies and are directed against the large extracellular domain of the transporter NaPi2b. Since the location of the N-terminal domain of NaPi2b in the cell has not been experimentally confirmed, this work aimed to analyze the recognition of the phosphate transporter NaPi2b in ovarian cancer cells OVCAR-4 and OVCAR-8 by antibodies against the N-terminal domain of the transporter using Western blot analysis and confocal microscopy.
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单克隆抗体N-NaPi2b在卵巢癌细胞中对钠依赖性磷酸盐转运体NaPi2b的识别
SLC34A2基因编码的钠依赖性磷酸共转运蛋白NaPi2b是一种跨膜蛋白,属于磷酸转运蛋白SLC34家族,参与维持人体磷酸稳态。磷酸转运蛋白NaPi2b在多种正常组织和机体器官中表达,在卵巢、肺、结直肠癌等恶性肿瘤中也表达。膜蛋白NaPi2b是肿瘤细胞中治疗性人源化抗体Rebmab200、XMT-1535和XMT-1536的靶标。这些抗体是在MX35抗体的基础上产生的,针对转运体NaPi2b的大胞外结构域。由于NaPi2b的n端结构域在细胞中的位置尚未得到实验证实,本工作旨在利用Western blot分析和共聚焦显微镜分析针对转运体n端结构域的抗体在卵巢癌细胞OVCAR-4和OVCAR-8中对磷酸转运体NaPi2b的识别。
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