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Development and validation of H11B2C2 monoclonal antibody-reactive hyaluronic acid binding protein: overexpression of HABP during human tumor progression

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Tumor Biology

An Erratum to this article was published on 14 December 2012

Abstract

Informative biomarkers of tumor progression have been elusive. The interaction between hyaluronic acid (HA) and its binding proteins (HABP) plays a pivotal role during malignancy. In the present study, we have developed a monoclonal antibody (mAb, termed as H11B2C2 mAb) and showed that this mAb specifically reacts with overexpressed HABP from a wide variety of malignant tumors as compared with benign tumors. In Western blot analysis, H11B2C2 mAb detected a major 80-kDa protein from human cancer cell lines, and the overexpression of 55–57- and 30-kDa proteins in malignant tumors compared with benign tumors. Furthermore, immunohistochemical analysis of different types of benign and malignant tumors with different grades showed higher expression of HABP in all the malignant tumors when compared with the benign tumors. HABP overexpression was specific to tumor cells when compared with the surrounding stroma and localized on the cell surface as well as in the intracellular region. The competitive inhibition experiments using HA polymer and its oligosaccharides in the Western blot and immunohistopathology experiments suggested that the H11B2C2 mAb-reactive protein is HABP. Altogether, the present study showed overexpression of the H11B2C2 mAb-reactive HABP in various malignant tumors as compared with benign tumors. Thus, H11B2C2 mAb-reactive HABP can be used as a potential biomarker during tumor progression.

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Acknowledgments

The authors acknowledge K.R Hospital, J.S.S Hospital, and Dr. Sri Ram at Bhagavan Pathology Laboratory for supplying tissue samples. We also thank Mr. Putnanju, for preparing tissue sections for the study; Dr. Satheesh Chencheri and Dr. Ragu Sinha, Penn State College of Medicine, for valuable suggestions during manuscript preparation; and Brooke Krovic and Dorthy Fiete for critical reading of the manuscript. Author R.K.B. is indebted to Dr. Chandra Mohan for his unrestricted inputs during this study.

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Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, UMDNJ-The Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ, 08903, USA

    Rajeev K Boregowda

  2. Department of Obstetrics and gynecology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Hitesh N. Appaiah

  3. Department of Biochemistry, University of Mysore, Mysore, India, 570006

    Mortha Karunakumar & Shibdas Banerjee

  4. Department of Pathology, Hassan Institute of Medical Sciences, Hassan, Karnataka, India, 573201

    Shivanna Parameshwariah

  5. Department of surgery, K.R. Hospital, Mysore, Karnataka, India, 570012

    Geetha Avadani

  6. Department of Pathology, J.S.S. Medical College, Mysore, Karnataka, India, 570020

    Sunila Sunila

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  1. Rajeev K Boregowda
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  2. Hitesh N. Appaiah
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Correspondence to Rajeev K Boregowda.

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Authors’ contributions

S.B., R.K.B., and M.K.K. designed the study. R.K.B. and H.N.A. performed experiments. S.B., R.K.B., S.P., and S.S. analyzed the results. S.P., S.S., and G.A. collected the tissue samples and clinical data. R.K.B., S.B., and S.P. contributed to the manuscript production.

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K Boregowda, R., Appaiah, H.N., Karunakumar, M. et al. Development and validation of H11B2C2 monoclonal antibody-reactive hyaluronic acid binding protein: overexpression of HABP during human tumor progression. Tumor Biol. 34, 597–608 (2013). https://doi.org/10.1007/s13277-012-0563-4

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