Targeting the oncofetal glyco-epitope TF blocks proliferation, migration and survival of breast cancer cell lines
Heublein S.1,2, Zhu J.2, Mayr D.3, Kuhn C.2, Hofmann S.2, Schindlbeck C.4, Schütz F.1, Jeschke U.2,5, Ditsch N.2,5
1Universitäts-Frauenklinik Heidelberg, Heidelberg, Deutschland, 2Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, München, Deutschland, 3Pathologisches Institut der Ludwig-Maximilians-Universität München, München, Deutschland, 4Frauenklinik Südostbayern, Traunstein, Deutschland, 5Frauenklinik der Universität Augsburg, Augsburg, Deutschland
Introduction: The Thomsen-Friedenreich (TF) antigen is a specific oncofetal carbohydrate (Galβ1-3GalNAcα1-) moiety that has been found to promote tumorigenesis. We investigated whether treatment of breast cancer (BC) cell lines with Nemod-TF1, a highly specific antibody targeting TF, influences proliferation, migration and apoptosis.
Methods: CAMA-1, MCF-7, ZR75-1 and MDA-MB-231 BC cell lines were used. Cells were treated with Nemod-TF1 (10, 30 or 60 µg/ml) or with a non-related IgM monoclonal antibody (Glycophorin) that served as control. Proliferation was measured by BrdU and migration by wound healing assay. In situ nick translation, cell death detection ELISA and M30 staining were used to assess different stages of apoptosis.
Results: Growth of all the four cell lines was significantly reduced in those samples incubated with Nemod-TF1. Nemod-TF1 was most potent in MCF-7 and reduced proliferation to 55 % of controls' level (p=0.002). Migration and apoptosis induction were studied in CAMA-1 and MCF-7 only. In MCF-7 closure of the scratch was significantly inhibited by Nemod-TF1 treatment (p=0.013), while regarding CAMA-1 this effect was of borderline significance. Both cell lines showed increased apoptosis rates when exposed to Nemod-TF1.
Conclusion: Nemod-TF1 blocked cell proliferation as well as migration and induced apoptosis. This observation fits with literature data from other cancer entities that link the TF epitope to cancer cell aggressiveness. However, mechanistic insights into how Nemod-TF1 alters TF activity remain to be determined.