Protein interactions with HER-family receptors can have different characteristics depending on the hosting cell line

Pavel Barta, Jennie Malmberg, Ludmila Melicharova, John Strandgård, Anna Orlova, Vladimir Tolmachev, Milan Laznicek, Karl Andersson

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Cell lines are common model systems in the development of therapeutic proteins and in the research on cellular functions and dysfunctions. In this field, the protein interaction assay is a frequently used tool for assessing the adequacy of a protein for diagnostic and therapeutic purposes. In this study, we investigated the extent to which the interaction characteristics depend on the choice of cell line for HER-family receptors. The interaction characteristics of two therapeutic antibodies (trastuzumab and cetuximab) and one Affibody molecule (Z HER2:342), interacting with the intended receptor were characterized with high precision using an automated real-time interaction method, in different cell lines (HaCaT, A431, HEP-G2, SKOV3, PC3, DU-145). Clear differences in binding affinity and kinetics, up to one order of magnitude, were found for the interaction of the same protein binding to the same receptor on different cells for all three proteins. For HER-family receptors, it is therefore important to refer to the measured affinity for a protein-receptor interaction together with the hosting cell line. The ability to accurately measure affinity and kinetics of a protein-receptor interaction on cell lines of different origins may increase the understanding of underlying receptor biology, and impact the selection of candidates in the development of therapeutic or diagnostic agents.

Original languageEnglish
Pages (from-to)1677-1682
Number of pages6
JournalInternational Journal of Oncology
Volume40
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Keywords

  • Affibody molecules
  • Affinity
  • Cetuximab
  • Epidermal growth factor receptor
  • HER2
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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