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      Podocalyxin is crucial for the growth of oral squamous cell carcinoma cell line HSC-2

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          Abstract

          Oral cancers constitute approximately 2% of all cancers, with the most common histological type being oral squamous cell carcinoma (OSCC), representing 90% of oral cancers. Although diagnostic technologies and therapeutic techniques have progressed, the survival rate of patients with OSCC is still 60%, whereas the incidence rate has increased. Podocalyxin (PODXL) is a highly glycosylated type I transmembrane protein that is detected in normal tissues such as heart, breast, and pancreas as well as in many cancers, including lung, renal, breast, colorectal, and oral cancers. This glycoprotein is associated with the progression, metastasis, and poor outcomes of oral cancers. PODXL overexpression was strongly detected using our previously established anti-PODXL monoclonal antibody (mAb), PcMab-47, and its mouse IgG 2a-type, 47-mG 2a. In previous studies, we also generated PODXL-knock out (PODXL-KO) cell lines using SAS OSCC cell lines, in order to investigate the function of PODXL in the proliferation of oral cancer cells. The growth of SAS/PODXL-KO cell lines was observed to be lower than that of parental SAS cells. For this study, PODXL-KO OSCC cell lines were generated using HSC-2 cells, and the role of PODXL in the growth of OSCC cell lines in vitro was assessed. Decreased growth was observed for HSC-2/PODXL-KO cells compared with HSC-2 parental cells. The influence of PODXL on tumor growth of OSCC was also investigated in vivo, and both the tumor volume and the tumor weight were observed to be significantly lower for HSC-2/PODXL-KO than that for HSC-2 parental cells. These results, taken together, indicate that PODXL plays an important role in tumor growth, both in vitro and in vivo.

          Highlights

          • •

            PODXL-knock out cell lines were established using HSC-2.

          • •

            The growth of HSC-2/PODXL-KO cells were lower than that of parental HSC-2.

          • •

            Tumor volumes of HSC-2/PODXL-KO cells were lower than that of HSC-2.

          • •

            PODXL has an important role in tumor growth in vitro and in vivo.

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          Oral Cavity Carcinoma: Current Management, Controversies, and Future Directions.

          Steven B. Chinn, Jeffrey N. Myers (2015)
          Oral cavity carcinoma (OCC) remains a major cause of morbidity and mortality in patients with head and neck cancer. Although the incidence has decreased over the last decade, outcomes remain stagnant with only a 5% improvement in overall survival in the last 20 years. Although surgical resection remains the primary treatment modality, several areas of controversy exist with regard to work-up, management of the primary and neck tumors, and adjuvant therapy. As surgical techniques evolve, so has the delivery of radiotherapy and systemic treatment, which have helped to improve the outcomes for patients with advanced disease. Recently, the addition of cetuximab has shown promise as a way to improve outcomes while minimizing toxicity, and this remains an active area of study in the adjuvant setting. Advances in microvascular free-flap reconstruction have extended the limits of resection and enabled enhanced restoration of function and cosmesis. While these advances have led to limited survival benefit, evaluation of alternative modalities has gained interest on the basis of success in other head and neck subsites. Organ preservation with definitive chemoradiotherapy, though proven in the larynx and pharynx, remains controversial in OCC. Likewise, although the association of human papillomavirus is well established in oropharyngeal carcinoma, it has not been proven in the pathogenesis or survival of OCC. Future study of the molecular biology and pathogenesis of OCC should offer additional insight into screening, treatment selection, and novel therapeutic approaches.
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            Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin

            Regis Doyonnas, David Kershaw, Christian Duhme … (2001)
            Podocalyxin is a CD34-related sialomucin that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of podocalyxin, we generated podocalyxin-deficient (podxl −/−) mice by homologous recombination. Null mice exhibit profound defects in kidney development and die within 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the podxl −/− mice, they fail to form foot processes and slit diaphragms and instead exhibit cell–cell junctional complexes (tight and adherens junctions). The corresponding reduction in permeable, glomerular filtration surface area presumably leads to the observed block in urine production. In addition, podxl −/− mice frequently display herniation of the gut (omphalocele), suggesting that podocalyxin may be required for retraction of the gut from the umbilical cord during development. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient mice, possibly through functional compensation by other sialomucins (such as CD34). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin could play a role in podocyte dysfunction in renal failure and omphalocele in humans.
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              The TRA-1-60 and TRA-1-81 human pluripotent stem cell markers are expressed on podocalyxin in embryonal carcinoma.

              William Dewolf, W Schopperle (2007)
              We have previously identified the cell adhesion protein podocalyxin expressed in a human pluripotent stem cell, embryonal carcinoma (EC), which is a malignant germ cell. Podocalyxin is a heavily glycosylated membrane protein with amino acid sequence homology to the hematopoietic stem cell marker CD34. Since the initial discovery of podocalyxin in a cancerous stem cell, numerous new studies have identified podocalyxin in many different human cancers and in embryonic stem cells lines (ES) derived from human embryos. Embryonal carcinoma, as do all human pluripotent stem cells, expresses TRA-1-60 and TRA-1-81 antigens, and although their molecular identities are unknown, they are commonly used as markers of undifferentiated pluripotent human stem cells. We report here that purified podocalyxin from embryonal carcinoma has binding activity with the TRA-1-60 and TRA-1-81 antibodies. Embryonal carcinoma cells treated with retinoic acid undergo differentiation and lose the TRA-1-60/TRA-1-81 markers from their plasma membrane surface. We show that podocalyxin is modified in the retinoic acid-treated cells and has an apparent molecular mass of 170 kDa on protein blots as compared with the apparent 200-kDa molecular weight form of podocalyxin expressed in untreated cells. Furthermore, the modified form of podocalyxin no longer reacts with the TRA-1-60/TRA-1-81 antibodies. Thus, embryonal carcinoma expresses two distinct forms of podocalyxin, and the larger version is a molecular carrier of the human stem cell-defining antigens TRA-1-60 and TRA-1-81.
              Article 0 comments Cited 49 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yukinari Kato
                Journal
                Journal ID (nlm-ta): Biochem Biophys Rep
                Journal ID (iso-abbrev): Biochem Biophys Rep
                Title: Biochemistry and Biophysics Reports
                Publisher: Elsevier
                ISSN (Electronic): 2405-5808
                Publication date PMC-release: 07 August 2018
                Publication date Collection: September 2018
                Publication date (Electronic): 07 August 2018
                Volume: 15
                Pages: 93-96
                Affiliations
                [a ]Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
                [b ]Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
                [c ]New Industry Creation Hatchery Center, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
                [d ]ZENOAQ RESOURCE CO., LTD., 1-1 Tairanoue, Sasagawa, Asaka-machi, Koriyama, Fukushima 963-0196, Japan
                [e ]Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, 18-24 Miyamoto, Numazu, Shizuoka 410-0301, Japan
                Author notes
                [* ]Corresponding author at: New Industry Creation Hatchery Center, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. yukinarikato@ 123456med.tohoku.ac.jp
                Article
                Publisher ID: S2405-5808(18)30170-5
                DOI: 10.1016/j.bbrep.2018.07.008
                PMC ID: 6086321
                SO-VID: 716e9ea1-28e6-406a-8437-5ee69f5edec7
                Copyright © © 2018 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 20 July 2018
                Date accepted : 27 July 2018
                Categories
                Subject: Research Article

                Keywords: oscc, oral squamous cell carcinoma,mab, monoclonal antibody,oral squamous cell carcinoma,oscc,hsc-2,podocalyxin,podxl,monoclonal antibody
                Data availability:
                Keywords: oscc, oral squamous cell carcinoma, mab, monoclonal antibody, oral squamous cell carcinoma, oscc, hsc-2, podocalyxin, podxl, monoclonal antibody

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