Research article

A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen

Sergei Rudchenko¹ , Matthew Scanlan² , Gavreel Kalantarov³ , Victoria Yavelsky⁴ , Chen Levy⁴ , Alison Estabrook³ , Lloyd Old² , Gerald L Chan⁵ , Leslie Lobel^{* 4} and Ilya Trakht^{* 3}

¹Hospital for Special Surgery, 535 East 70th Street, New York NY 10021, USA

²Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA

³College of Physicians and Surgeons, Columbia University, 630 W. 168 St., New York, NY 10032, USA

⁴Department of Virology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel

⁵The Morningside Foundation, 1188 Centre Street, Newton Centre, MA 02459, USA

author email corresponding author email* Contributed equally

BMC Cancer 2008, 8:248doi:10.1186/1471-2407-8-248

Published:	24 August 2008

Abstract

Background

We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients.

Methods

The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification.

Results

By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein.

Conclusion

We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification.