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Glycobiology Advance Access published online on June 15, 2009
Glycobiology, doi:10.1093/glycob/cwp085
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A newly generated functional antibody identifies Tn antigen as a novel determinant in cancer cell-lymphatic endothelium interaction.

Carla Danussi1,2,3, Anna Coslovi2, Cristiana Campa4,#, Maria T. Mucignat1, Paola Spessotto1, Fulvio Uggeri5, Sergio Paoletti2 and Alfonso Colombatti1,3,6*

1 Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, 33081 Aviano, Pordenone, Italy
2 Department of Life Sciences, University of Trieste, 34100 Trieste, Italy
3 Department of Biomedical Sciences and Technologies, University of Udine, 33100 Udine, Italy
4 Bracco Imaging SpA-CRB Trieste, AREA Science Park, 34100 Trieste, Italy
5 Bracco Imaging SpA, 20134 Milan, Italy
6 MATI Center of Excellence, University of Udine, 33100 Udine, Italy

* Corresponding author. Mailing address: Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS; via F. Gallini 2; 33081 Aviano, Pordenone; Italy. Phone: +39 0434 659 365. Fax: +39 0434 659 428. E-mail: acolombatti{at}cro.it.

Received on May 4, 2009; accepted on June 10, 2009

Malignant transformation of epithelial cells is frequently associated with the alteration of glycosilation pathways. Tn is a common Tumor-Associated Carbohydrate Antigen (TACA) present in 90% of human carcinomas and its expression correlates with metastatic potential and poor prognosis. Despite its relevance, the functional role of Tn in tumor biology has not been firmly established probably for the lack of appropriate experimental tools. Our aims were to produce highly reactive monoclonal antibodies (mAbs) against Tn making use of synthetically produced Tn and to test their usefulness for in vivo imaging as well as to define their potential functional activity in tumor cell spread. We immunized mice with Tn clustered on cationized BSA and screened the positive hybridomas with Tn-biotinylated alginate. ELISA and immunofluorescence assays revealed that the most reactive anti-Tn IgM mAb (2154F12A4) selectively recognized Tn on MCF7 breast cancer cell line, since its binding to the cell membrane was completely abolished by preincubation with purified Tn. Importantly, QDot 800-conjugated mAb injected in MCF7-tumor bearing mice specifically bound to primary tumor lesions as well as to metastases in lymph nodes. In addition, this mAb was able to inhibit cancer cell adhesion to lymphatic endothelium suggesting a novel involvement of Tn in the lymphatic dissemination of cancer cells and hypothesizing future applications in inhibiting lymphatic metastases.

Key words: in vivo imaging / lymphatic endothelial cells / metastasis / monoclonal antibody / Tn antigen

# present address: Novartis Vaccines & Diagnostics, Technology Development, 53100 Siena, Italy


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