Biochemical and Biophysical Research Communications
Validation of HB-EGF and amphiregulin as targets for human cancer therapy
Section snippets
Materials and methods
Reagents. Diphtheria toxin was prepared as described previously [9]. All the siRNAs for EGFR ligands and EGFR were purchased from TaKaRa Bio Inc. (Shiga, Japan). Polyclonal rabbit anti-EGFR (sc03) and anti-ERK1/2 antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA). Mouse monoclonal antibodies against phospho-tyrosine clone 4G10 and phospho-MAPK were acquired from Upstate Biotechnology Inc. (Lake Placid, NY).
Cells and cell culture. The following cell lines were obtained
mRNA expression of EGFR ligands, EGFR, and ErbB2 as well as secretion of EGFR ligand proteins in cancer cell lines
HB-EGF or amphiregulin was identified as the primarily predominant EGFR ligand in most of cancer cells, whereas the expression levels of the other EGFR ligands appeared to vary (Fig. 1A and B, and Supplemental Fig. 1A–L). In ovarian, gastric, bladder, and breast cancers, malignant melanoma and glioblastoma cells with high expression of HB-EGF mRNA, and abundant secretion of soluble HB-EGF were found (Fig. 2A and Supplemental Fig. 2A). In colon, pancreatic, and prostate cancer, renal cell
Discussion
In the present study, we have confirmed the validity of HB-EGF and amphiregulin as targets for cancer therapy (Supplemental Table 1). HB-EGF and amphiregulin possess a heparin-binding motif, whereas the other EGFR ligands do not [7]. Accordingly, HB-EGF and amphiregulin have quite an advantage toward accumulating on the cell surface and activating the EGFR pathway through binding to heparin sulfate proteoglycans (HSPGs) compared to other EGFR ligands without the motif, although a difference
Acknowledgments
This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (No. 17014057) and Research Promotion for Innovative Therapies against Cancers from the Ministry of Education, Culture, Sports, Science and Technology to E.M.
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