61P - Nectin4 effects in the tumor phenotype

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Abderrezak Ghidouche
Citation Annals of Oncology (2015) 26 (suppl_3): 15-24. 10.1093/annonc/mdv117
Authors A. Ghidouche1, L. Marc2, R. Castellano2, D. Olive2
  • 1Laboratoire De Recherche En Génie Biologique Des Cancers, Université de Bejaia, Bejaia/DZ
  • 2Centre De Recherche En Cancérologie De Marseille, Centre de Recherche en Cancérologie de Marseille, Marseille/FR

Abstract

Body

Nectin-4 is a transmembrane immunoglobulin of the nectin familly. It is weakly expressed in healthy tissues, in contrast with embryonic stage. Interestingly, an expression of nectin-4 is found in breast, ovarian and lung tumors. The intensity of tissue expression of nectin-4 is correlated to the advanced stages of these cancerous pathologies. Furthermore, high levels of the plasmatic form are also found at an important rate in the advanced stages of breast, ovarian and lung carcinomas. To identify roles of nectin -4 expression in tumor progression, we aimed to study cell growth, migration and invasion, both in vitro and in vivo. We used breast cancer cell lines MCF-7 and BT-474 expressing an endogenous nectin-4, but also MDA-MB213 cell lines transfected with native forms of nectin-4 (MDA-MB213 R4. C1) or with a form of nectin-4 truncate of eight amino acids at juxta-membrane domain (MDA-MB231 Del8.6). We observed that the MDA-MB231 R4.C1 and MDA-MB231 Del8.6 cells, have high growth capacities (p > 0.005). But this growth seems more important in drastic middle conditions (0% FCS) only for MDA-MB231 R4.C1 cells. Using monoclonal antibodies targeting the extracellular domain of nectin-4, we observed significant (p> 0.005) diminution of cell growth for BT-474 cell line and MCF-7 cell line when using a specific siRNA. Nectin-4 is also implicated in the increase of the cellular migration. Indeed, cells expressing nectin-4 show a migration capability higher than about 66 % compared with MDA-MB231 wt cells and it seems that the soluble form does not influence cell migration intensity.The use of a monoclonal antibody anti-nectin-4 led to a reduction in the migration of MDA-MB231 R4.C1 cells. For the cell clonogenicity power, we observed an effect on MDA-MB-231 R4.C1 cells compared with MDA-MB231 wt and MDA-MB231 Del8.6 cells. In vivo, on MDA-MB231 wt and MDA-MB231 R4.C1 xenograft NOG mouse, the expression of nectin-4 significantly increased tumoral volume as well as the metastatic power. Anti-nectin-4 antibody does not affect tumor growth, but seems to decrease metastatic potential. In vitro & in vivo results seem to demonstrate that the cell surface expression of nectin-4 but also the soluble form are involved on tumorigenicity.

Disclosure: All authors have declared no conflicts of interest.