Identification of phosphate transporter NaPi2b as MX35 cancer antigen by modified SEREX approach

Kiyamova, Ramziya; Gryshkova, Vitalina; Usenko, V. S.; Khozaenko, Y. S.; Gurtovyy, V. A.; Yin, Beatrice W.T.; Ritter, Gerd; Old, Lloyd J.; Gout, Ivan; Filonenko, Valeriy

doi:10.7124/bc.0007a3

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Our results are in accordance with the published data. Upregulation in myeloid and bowel tumors was found in several studies [ 35 , 36 ]; the overexpression of SLC34A2 was found in endometrioid and papillary serous ovarian carcinomas [ 14 , 15 , 16 , 37 , 38 ], and it was shown that in uterine (endometrial) cancer, SLC34A2 expression appeared relatively increased [ 14 , 16 ]. Downregulation in breast [ 39 ], liver [ 40 ], and lung [ 7 , 8 , 9 ] tumors was discovered in several studies.…”

Section: Discussionmentioning

confidence: 99%

“…An altered expression of sodium-dependent phosphate transporter NaPi2b has been reported in ovarian cancer [ 6 ], lung cancer [ 7 , 8 , 9 , 10 ], gastric cancer [ 11 ], thyroid cancer [ 12 ], and other cancers [ 13 ]. The phosphate transporter NaPi2b was identified as a target for MX35 monoclonal antibodies using modified SEREX (the serological analysis of recombinant cDNA expression libraries) technology [ 14 , 15 ]. Currently, NaPi2b is a target for therapeutic antibodies XMT-1536 and XMT-1592, which are in clinical trials for the treatment of ovarian and lung cancers [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

et al. 2021

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The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

et al. 2021

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“…Therefore, the identification and characterization of new molecular markers for diagnosis and more accurate prediction of sensitivity to chemotherapy, including targeted chemotherapy, as well as the course and outcome of the disease, is an urgent task. The sodium-dependent phosphate transporter NaPi2b was identified as a target for MX35 monoclonal antibodies using a modified SEREX technology [ 9 , 10 ]. NaPi2b is overexpressed in 90% of epithelial ovarian cancer and other human malignancies including thyroid, lung, breast, and other cancers [ [11] , [12] , [13] ].…”

Section: Introductionmentioning

confidence: 99%

Sodium-dependent phosphate transporter NaPi2b as a potential predictive marker for targeted therapy of ovarian cancer

Nurgalieva¹,

Popov²,

Skripova³

et al. 2021

Biochemistry and Biophysics Reports

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The high mortality rate from ovarian cancer is due to the asymptomatic nature of the course of the disease, which leads to the diagnosis of ovarian cancer in later stages. The sodium-dependent phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80–90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we aimed to evaluate NaPi2b as a molecular marker for diagnostics and predicting the course and outcome of ovarian cancer disease. Quantitative analysis of SLC34A2 gene expression in ovarian tumor tissue was performed at the level of transcription and translation using real-time PCR, droplet digital PCR and Western blot analysis respectively. Statistical analysis was performed taking into account various clinicopathological characteristics of the ovarian cancer patients, including the stage of the disease, the tumor grade, the applying of neoadjuvant chemotherapy and the presence of ascites. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer.

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Recognition of mutant forms of the sodium-dependent phosphate transporter NaPi2b by monoclonal antibodies in ovarian cancer cells

et al. 2022

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Background. The sodium-dependent phosphate transporter NaPi2b is expressed in a number of tumors and serves as a target for monoclonal antibody therapy. The NaPi2b transporter has a large extracellular domain containing 4 cysteines and an MX35 epitope recognized by the corresponding monoclonal antibodies. Aim. To study the recognition of the MX35 epitope in cysteine mutants C303 and C350 of the sodium-dependent phosphate transporter NaPi2b by monoclonal antibodies in ovarian cancer cells. Material and methods. Ovarian cancer cells of the OVCAR-8 line were transfected with plasmids encoding mutant forms of the NaPi2b transporter. The recognition of these forms by monoclonal antibodies was studied by Western blot and flow cytometry. Statistical analysis of flow cytometry data was performed using Pearsons Chi-squared test with Yates correction. Results. Western blot analysis of lysates of OVCAR-8 cells expressing the wild-type NaPi2b transporter demonstrated the presence of a specific signal only in samples without the addition of dithiothreitol, while in all samples with NaPi2b cysteine mutants, even without the addition of dithiothreitol, no specific signal from monoclonal antibodies was detected. The flow cytometry results showed that proportion of OVCAR-8 cells with positive staining of the MX35 epitope with antibodies is less when expressing the NaPi2b mutants compared to the wild type. Conclusion. Cysteines C303 and C350 are involved in disulfide bonds formation, which is of key importance for the formation of the conformation of the extracellular domain of the sodium-dependent phosphate transporter NaPi2b, which ensures the MX35 epitope recognition by monoclonal antibodies.

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Identification of phosphate transporter NaPi2b as MX35 cancer antigen by modified SEREX approach

Cited by 5 publications

References 25 publications

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

Sodium-dependent phosphate transporter NaPi2b as a potential predictive marker for targeted therapy of ovarian cancer

Recognition of mutant forms of the sodium-dependent phosphate transporter NaPi2b by monoclonal antibodies in ovarian cancer cells

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Identification of phosphate transporter NaPi2b as MX35 cancer antigen by modified SEREX approach

Cited by 5 publications

References 25 publications

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

Sodium-dependent phosphate transporter NaPi2b as a potential predictive marker for targeted therapy of ovarian cancer

Recognition of mutant forms of the sodium-dependent phosphate transporter NaPi2b by ­monoclonal antibodies in ovarian cancer cells

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Recognition of mutant forms of the sodium-dependent phosphate transporter NaPi2b by monoclonal antibodies in ovarian cancer cells