Heparin-Binding EGF-Like Growth Factor Is a Promising Target for Ovarian Cancer Therapy

Abstract

Ovarian cancer is the most frequent cause of cancer death among all gynecologic cancers. We demonstrate here that lysophosphatidic acid (LPA)-induced ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF) is a critical to tumor formation in ovarian cancer. We found that among the epidermal growth factor receptor (

Heparin‐binding epidermal growth factor‐like growth factor as a novel targeting molecule for cancer therapy

“…E-mail: emekada@biken.osaka-u.ac.jp Abbreviations: EGF, epidermal growth factor; EGFR, EGF receptor; ERK, extracellular regulated kinase; GPCR, G protein-coupled receptor; HB-EGF, heparinbinding epidermal growth factor-like growth factor; MAPK, mitogen-activated protein kinase; proHB-EGF, membrane-anchored form of HB-EGF; sHB-EGF, soluble form of HB-EGF; TGF-α, transforming growth factor-α. (6,7) In this review, we will describe the features of HB-EGF as a candidate target for cancer therapy. We will also discuss the future directions for the development of therapeutic strategies targeting HB-EGF.…”

“…There is growing evidence of increased HB-EGF expression in tumors, including pancreatic, liver, esophageal, melanoma, colon, gastric, ovarian and bladder cancers as well as glioblastoma, compared with normal tissues (6,11,48,63,64) (S . Miyamoto et al, unpublished observation, 2005).…”

“…A number of tumors isolated from ovarian cancer patients express high levels of HB-EGF, and ascitic fluid obtained from ovarian cancer patients contains higher concentrations of HB-EGF protein than the concentrations found in normal control subjects and patients with benign tumors. (6,7) Furthermore, the expression levels of other EGFR ligands in ovarian cancer samples and the protein levels in ascitic fluid from ovarian cancer patients are one or two orders of magnitude lower than those of HB-EGF. It has also been shown that HB-EGF expression is significantly associated with the clinical outcome in ovarian cancer (7) (Fig.…”

Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively

“…AR and HB-EGF are upregulated in breast (LeJeune et al, 1993;Normanno et al, 1995;Salomon et al, 1995;Panico et al, 1996;Visscher et al, 1997), prostate (Bostwick et al, 2004), and gastric cancers (Cook et al, 1992;Kitadai et al, 1993;Ebert et al, 1994;Normanno et al, 1995) and keratinocytic tumors (Billings et al, 2003). Shedding of HB-EGF is a critical step in tumor formation (Miyamoto et al, 2004), and overexpression of AR promotes growth of keratinocytic tumors (Billings et al, 2003).…”

Toward an Integrative Analysis of the Tumor Microenvironment in Ovarian Epithelial Carcinoma

“…This growth factor is highly expressed proportionately as disease pathology progresses, yielding high concentrations in advanced stages and ascites in particular [79]. HB-EGF contains a heparan sulfate binding motif that enables its binding to heparan sulfate proteoglycans (HSPG) in the coelomic epithelium.…”