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      Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer

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          Abstract

          Ovarian cancer has a high recurrence rate after platinum‐based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer‐specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV‐3, and generated hybridoma clones. Several rounds of screening yielded 30 monoclonal antibodies (mAbs) with no cross‐reactivity to normal cells. Among these mAbs, OV‐Ab 30‐7 was found to target integrin α3 and upregulate p53 and p21, while stimulating the apoptosis of cancer cells. We further found that binding of integrin α3 by OV‐Ab 30‐7 impaired laminin‐induced focal adhesion kinase phosphorylation. The mAb alone or in combination with carboplatin and paclitaxel inhibited tumor progression and prolonged survival of tumor‐bearing mice. Moreover, immunohistochemical staining of ovarian patient specimens revealed higher levels of integrin α3 in cancer cells compared with normal cells. By querying online clinical databases, we found that elevated ITGA3 expression in ovarian cancer is associated with poor prognosis. Taken together, our data suggest that the novel mAb, OV‐Ab 30‐7, may be considered as a potential therapeutic for ovarian cancer.

          Abstract

          The novel mAb, OV‐Ab 30‐7, can induce ovarian cancer cell apoptosis, and blockage integrin‐laminin signaling, and may be considered as a potential therapeutic for ovarian cancer.

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          Most cited references67

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          Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

          The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
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            Integrin-regulated FAK-Src signaling in normal and cancer cells.

            Integrins can alter cellular behavior through the recruitment and activation of signaling proteins such as non-receptor tyrosine kinases including focal adhesion kinase (FAK) and c-Src that form a dual kinase complex. The FAK-Src complex binds to and can phosphorylate various adaptor proteins such as p130Cas and paxillin. In normal cells, multiple integrin-regulated linkages exist to activate FAK or Src. Activated FAK-Src functions to promote cell motility, cell cycle progression and cell survival. Recent studies have found that the FAK-Src complex is activated in many tumor cells and generates signals leading to tumor growth and metastasis. As both FAK and Src catalytic activities are important in promoting VEGF-associated tumor angiogenesis and protease-associated tumor metastasis, support is growing that FAK and Src may be therapeutically relevant targets in the inhibition of tumor progression.
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              Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer.

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                Author and article information

                Contributors
                pathologykimo@gmail.com
                hcw0928@gate.sinica.edu.tw
                Journal
                Cancer Sci
                Cancer Sci
                10.1111/(ISSN)1349-7006
                CAS
                Cancer Science
                John Wiley and Sons Inc. (Hoboken )
                1347-9032
                1349-7006
                07 August 2020
                October 2020
                : 111
                : 10 ( doiID: 10.1111/cas.v111.10 )
                : 3478-3492
                Affiliations
                [ 1 ] Institute of Cellular and Organismic Biology Academia Sinica Taipei Taiwan
                [ 2 ] Graduate Institute of Pathology College of Medicine National Taiwan University Taipei Taiwan
                [ 3 ] Department of Pathology National Taiwan University Hospital Taipei Taiwan
                [ 4 ] Department of Pathology and Laboratory Medicine National Taiwan University Hospital Hsin‐Chu Biomedical Park Branch Hsinchu County Taiwan
                Author notes
                [*] [* ] Correspondence

                Kuan-Ting Kuo, Department of Pathology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan.

                Email: pathologykimo@ 123456gmail.com

                Han-Chung Wu, Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Academia Road, Section 2, Nangang, Taipei 11529, Taiwan

                Email: hcw0928@ 123456gate.sinica.edu.tw

                Author information
                https://orcid.org/0000-0002-3657-1652
                https://orcid.org/0000-0002-5185-1169
                Article
                CAS14566
                10.1111/cas.14566
                7541015
                32648337
                e6b4e8a6-6fab-4b90-b86f-c3cd5d428798
                © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 15 April 2020
                : 24 June 2020
                : 02 July 2020
                Page count
                Figures: 5, Tables: 0, Pages: 15, Words: 9751
                Funding
                Funded by: National Taiwan University , open-funder-registry 10.13039/501100006477;
                Award ID: NTU‐CDP‐103R7837
                Funded by: Program for Translational Innovation of Biopharmaceutical Development ‐ Technology Supporting Platform Axis
                Award ID: 107‐0210‐01‐19‐04
                Funded by: Ministry of Science and Technology , open-funder-registry 10.13039/100007225;
                Award ID: MOST‐108‐2823‐8‐001‐001
                Award ID: MOST‐108‐3114‐Y‐001‐002
                Funded by: Academia Sinica , open-funder-registry 10.13039/501100001869;
                Award ID: AS‐SUMMIT‐108
                Categories
                Original Article
                Basic and Clinical Immunology
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.2 mode:remove_FC converted:07.10.2020

                Oncology & Radiotherapy
                cell apoptosis,focal adhesion kinase,integrin α3,laminin,monoclonal antibody,ovarian cancer

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