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Epidermal Growth Factor-like Growth Factor (epidermal + growth_factor-like_growth_factor)
Selected AbstractsInfiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF)JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2002Tadanori Mammoto Although the mechanism is unknown, infiltration anesthetics are believed to have membrane-stabilizing action. We report here that such a most commonly used anesthetic, lidocaine, effectively inhibited the invasive ability of human cancer (HT1080, HOS, and RPMI-7951) cells at concentrations used in surgical operations (5,20 mM). Ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) from the cell surface plays an important role in invasion by HT1080 cells. Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2+ concentration contributed to this action. The anesthetic action of lidocaine (sodium channel blocking ability) did not contribute to this anti-invasive action. In addition, lidocaine (5,30 mM), infiltrated around the inoculation site, inhibited pulmonary metastases of murine osteosarcoma (LM 8) cells in vivo. These data point to previously unrecognized beneficial actions of lidocaine and suggest that lidocaine might be an ideal infiltration anesthetic for surgical cancer operations. © 2002 Wiley-Liss, Inc. [source] An integrated view of L-selectin and trophinin function in human embryo implantationJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2008Michiko N. Fukuda Determining molecular mechanisms of human embryo implantation is an extremely challenging task due to the limitation of materials and significant differences underlying this process among mammalian species. Recently, L-selectin and its ligand carbohydrate have been proposed as a system that mediates initial adhesion of human blastocysts to the uterine epithelia. We have also identified trophinin as a unique apical cell adhesion molecule potentially involved in the initial adhesion of trophectoderm of the human blastocyst to endometrial surface epithelia. In the mouse, the binding between ErbB4 on the blastocyst and heparin-binding epidermal growth factor-like growth factor on the endometrial surface enables the initial step of the blastocyst implantation. The evidence suggests that L-selectin and trophinin are included in human embryo implantation. This review summarizes findings relevant to the functions of L-selectin and trophinin in human embryo implantation, and proposes a model that reconciles these cell adhesion mechanisms. [source] Decidualization and implantation: Embryo-uterine bioinformatics at workMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2001Abraham L. Kierszenbaum The implantation of the blastocyst into a nurturing endometrium involves two overlapping steps: 1. The blastocyst-endometrial luminal epithelial attachment. 2. The decidualization of the endometrial stroma. An intriguing question is how does the blastocyst identify the uterine implantation site. Current research is focused on hypothetical soluble signaling molecules released by the blastocyst for conditioning a discrete uterine luminal epithelial domain for implantation. A still unresolved issue is the functional significance of receptor autophosphorylation following binding of uterine epithelial cell-derived heparin-binding epidermal growth factor-like growth factor to the epidermal growth factor receptor on trophoectodermic cell surfaces. With recent results hinting at the role of signaling proteins associated with the bone morphogenetic protein, fibroblast growth factor, WNT and hedgehog families to enable embryo implantation, the dynamics of uterine-embryo interaction becomes linked to fundamental cellular pathways of growth, differentiation and apoptosis. Mol. Reprod. Dev. 59:123,125, 2001. © 2001 Wiley-Liss, Inc. [source] Upregulation of heparin-binding epidermal growth factor-like growth factor and osteopontin in experimental hydronephrosisNEPHROLOGY, Issue 3 2000M Katerelos SUMMARY This study examined the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and osteopontin in unilateral ureteral obstruction (UUO) in the rat, a model of obstructive uropathy. HB-EGF mRNA was upregulated 5.5-fold at 4 h post-obstruction (P < 0.05) and 4.5-fold after 12 h (P < 0.05). Immunohistochemical staining for HB-EGF demonstrated an increase in protein in the distended tubules. To determine what effects increased HB-EGF might have in the obstructed kidney, we attempted to determine whether HB-EGF upregulates osteopontin and ,-smooth muscle actin (,-SMA) in the tubular line NRK-52E. Both of these molecules are increased in UUO. Osteopontin mRNA was upregulated in NRK-52E cells after 24, 48 and 72 h HB-EGF stimulation. In contrast, HB-EGF caused a downregulation of ,-SMA protein by Western blot in NRK-52E cells. When a blocking mAb against secreted HB-EGF was administered, however, there was no effect on osteopontin mRNA levels or immunohistochemical staining for ,-smooth muscle actin. These data suggest that the action of HB-EGF in UUO may be to increase osteopontin and reduce ,-smooth muscle actin expression by tubular epithelial cells by an autocrine or intracrine mechanism. By reducing ,-SMA expression, HB-EGF may also act to maintain epithelial cell morphology in this model. [source] Heparin-binding epidermal growth factor-like growth factor functionally antagonizes interstitial cystitis antiproliferative factor via mitogen-activated protein kinase pathway activationBJU INTERNATIONAL, Issue 4 2009Jayoung Kim OBJECTIVE To delineate the mechanism underlying the potential functional relationship between interstitial cystitis antiproliferative factor (APF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), as APF has previously been shown to decrease the proliferation rate of normal bladder epithelial cells and the amount of HB-EGF produced by these cells. MATERIALS AND METHODS APF-responsive T24 transitional carcinoma bladder cells were treated with high-pressure liquid chromatography-purified native APF with or without HB-EGF to determine the involvement of signalling pathways and proliferation by Western blot analysis, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (Erk)/MAPK assays, and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS Cyclic stretch induced the secretion of HB-EGF from T24 cells overexpressing the HB-EGF precursor, resulting in enhanced proliferation. T24 cells treated with APF had increased p38MAPK activity and suppressed cell growth, events that were both reversed by treatment with a p38MAPK-selective inhibitor. Activation of Erk/MAPK by HB-EGF was inhibited by APF, and APF did not stimulate p38MAPK in the presence of soluble HB-EGF or when cells overexpressed constitutively secreted HB-EGF. Lastly, APF inhibitory effects on cell growth were attenuated by HB-EGF. CONCLUSIONS These results indicate that HB-EGF and APF are functionally antagonistic and signal through parallel MAPK signalling pathways in bladder cells. [source] Heparin-binding epidermal growth factor-like growth factor isoforms and epidermal growth factor receptor/ErbB1 expression in bladder cancer and their relation to clinical outcomeCANCER, Issue 10 2007Christopher Kramer MD Abstract BACKGROUND. Cleavage of membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields a soluble HB-EGF isoform (sHB-EGF), which is an activating epidermal growth factor receptor (EGFR) ligand and a C-terminal fragment HB-EGF-C acting directly in the nucleus. In bladder cancer, overexpression of both HB-EGF and EGFR have been observed, but to the authors' knowledge the prognostic significance of different modes of HB-EGF signaling have remained unclear. METHODS. Expression and intracellular localization of HB-EGF and EGFR were examined by immunohistochemistry in paraffin-embedded specimens from 121 patients who underwent cystectomy for bladder cancer. Tumor stage was pTis/pT1 in 7 patients, pT2 in 41 patients, pT3 in 55 patients, and pT4 in 18 patients. Lymph node metastases were present in 32 patients. RESULTS. Using an antibody directed against the C-terminal domain, HB-EGF expression was detected in the cytoplasm or in the nucleus of tumor cells. EGFR staining was uniform at the plasma membrane. The actuarial 5-year cancer-specific survival of patients with tumors with predominant nuclear HB-EGF staining was 28% compared with 57% if HB-EGF staining was predominantly cytoplasmic (P = .027). Disease outcome of patients with a ,mixed' HB-EGF staining pattern was found to be between that of the 2 former groups. In agreement with previous studies, strong EGFR expression was associated with poor prognosis. Despite strong EGFR expression, predominant cytoplasmic HB-EGF staining was associated with a more favorable outcome, whereas a predominant nuclear pattern defined a subgroup with extremely poor prognosis (5-year tumor-specific survival of 55% vs 13%, respectively; P = .026). CONCLUSIONS. The current study results confirm that EGFR expression is significantly correlated with disease-specific mortality but that the outcome is also influenced by the mode of HB-EGF signaling. Additional nuclear HB-EGF signaling, indicative of increased cleavage of proHB-EGF, appears to enhance the adverse activities. Cytoplasmic HB-EGF staining likely reflects proHB-EGF, which may also exert antiproliferative effects. Cancer 2007. © 2007 American Cancer Society. [source] Heparin-binding epidermal growth factor-like growth factor as a novel targeting molecule for cancer therapyCANCER SCIENCE, Issue 5 2006Shingo Miyamoto HB-EGF, a member of the EGF family of growth factors, exerts its biological activity through activation of the EGFR and other ErbB receptors. HB-EGF participates in diverse biological processes, including heart development and maintenance, skin wound healing, eyelid formation, blastocyst implantation, progression of atherosclerosis and tumor formation, through the activation of signaling molecules downstream of ErbB receptors and interactions with molecules associated with HB-EGF. Recent studies have indicated that HB-EGF gene expression is significantly elevated in many human cancers and its expression level in a number of cancer-derived cell lines is much higher than those of other EGFR ligands. Several lines of evidence have indicated that HB-EGF plays a key role in the acquisition of malignant phenotypes, such as tumorigenicity, invasion, metastasis and resistance to chemotherapy. Studies in vitro and in vivo have indicated that HB-EGF expression is essential for tumor formation of cancer-derived cell lines. CRM197, a specific inhibitor of HB-EGF, and an antibody against HB-EGF are both able to inhibit tumor growth in nude mice. These results indicate that HB-EGF is a promising target for cancer therapy, and that the development of targeting tools against HB-EGF could represent a novel type of therapeutic strategy, as an alternative to targeting ErbB receptors. (Cancer Sci 2006; 97: 341,347) [source] | |||||||||||||