EGFR and ErbB2 are functionally coupled to CD44 and regulate shedding, internalization and motogenic effect of CD44
| Autor: | János Szöllosi, Hideyuki Saya, Zsuzsanna Pályi-Krekk, Tamás Kovács, Péter Nagy, Osamu Nagano, Márk Barok |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
animal structures Receptor ErbB-2 Neuregulin-1 media_common.quotation_subject Mice SCID Antibodies Monoclonal Humanized Receptor tyrosine kinase Mice ErbB Receptors Cell Movement ErbB Trastuzumab Epidermal growth factor Cell Line Tumor medicine Animals Humans Hyaluronic Acid skin and connective tissue diseases Internalization neoplasms Adaptor Proteins Signal Transducing media_common biology Chemistry Antibodies Monoclonal Hyaluronan Receptors Oncology Cancer research biology.protein Neuregulin Pertuzumab Neoplasm Transplantation medicine.drug |
| Zdroj: | Cancer Letters. 263:231-242 |
| ISSN: | 0304-3835 |
| Popis: | Activation of the ErbB family of receptor tyrosine kinases is involved in a range of human cancers. Transmembrane signaling mediated by ErbB proteins is stimulated by peptide growth factors and is blocked by monoclonal antibodies such as trastuzumab and pertuzumab. ErbB receptors exert their function in conjunction with non-ErbB proteins, e.g. CD44. Here we show that epidermal growth factor (EGF) and heregulin induce CD44 shedding in JIMT-1, an ErbB2-overexpressing cell line resistant to trastuzumab, accompanied by internalization and intramembrane proteolysis of CD44 and enhanced cellular motility. These effects of EGF and heregulin are blocked by pertuzumab. Trastuzumab inhibits the heregulin- and hyaluronan oligosaccharide-induced shedding and internalization of CD44 and their motogenic effect. Trastuzumab also blocks CD44 shedding from JIMT-1 xenograft tumors in vivo. At the same time the internalization rate of trastuzumab is increased by hyaluronan oligosaccharide treatment in vitro. Our experiments point to an unexpected, but potentially important mechanism of action of ErbB receptor-targeted monoclonal antibodies used in the treatment of cancer. |
| Databáze: | OpenAIRE |
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