Epidermal growth factor signalling and bone metastasis

Epidermal growth factor (EGF) signalling is well known for its multifaceted functions in development and tissue homoeostasis. The EGF family of ligands and receptors (ERBB family) have also been extensively investigated for their roles in promoting tumourigenesis and metastasis in a variety of cancer types. Recent findings indicate that EGF signalling is an important mediator of bone metastasis in breast, prostate and kidney cancers. The EGF signalling stimulates the growth of bone metastasis directly by increasing tumour cell proliferation and indirectly by engaging bone stromal cell in metastasis-promoting activities. Therefore, molecular targeting of ERBB receptors may benefit patients with bone metastasis and should be evaluated in clinical trials.

[1]  R. Derynck,et al.  Human recombinant transforming growth factor alpha stimulates bone resorption and inhibits formation in vitro. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[2]  H. Lane,et al.  ERBB Receptors and Cancer: The Complexity of Targeted Inhibitors , 2005, Nature Reviews Cancer.

[3]  N. Normanno,et al.  Epidermal growth factor receptor (EGFR) signaling in cancer. , 2006, Gene.

[4]  R. Cardiff,et al.  Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[5]  G. Roodman.  Mechanisms of bone metastasis. , 2004, Discovery medicine.

[6]  A. Citri,et al.  EGF–ERBB signalling: towards the systems level , 2006, Nature Reviews Molecular Cell Biology.

[7]  F. Zhan,et al.  The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. , 2003, The New England journal of medicine.

[8]  P. Fasching,et al.  A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer , 2004, Breast Cancer Research and Treatment.

[9]  E. Wagner,et al.  Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart , 2003, Development.

[10]  L. Raisz,et al.  Effects of DNA and prostaglandin synthesis inhibitors on the stimulation of bone resorption by epidermal growth factor in fetal rat long-bone cultures. , 1986, The Journal of clinical investigation.

[11]  N. Normanno,et al.  The role of the EGFR signaling in tumor microenvironment , 2008, Journal of cellular physiology.

[12]  Qiongqing Wang,et al.  ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. , 2009, Genes & development.

[13]  M. Moasser,et al.  The epidermal growth factor receptor family: Biology driving targeted therapeutics , 2008, Cellular and Molecular Life Sciences.

[14]  David L. Lacey,et al.  Osteoclast differentiation and activation , 2003, Nature.

[15]  Wei Wei,et al.  Metastatic patterns in adenocarcinoma , 2006, Cancer.

[16]  Yibin Kang,et al.  IMPLICATIONS FOR OSTEOLYTIC BONE METASTASES * , 2007, Journal of Biological Chemistry.

[17]  B. Hogan,et al.  Development of mammary hyperplasia and neoplasia in MMTV-TGFα transgenic mice , 1990, Cell.

[18]  N. Normanno,et al.  Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis. , 2005, Endocrine-related cancer.

[19]  R. Derynck,et al.  Recombinant human transforming growth factor-alpha stimulates the formation of osteoclast-like cells in long-term human marrow cultures. , 1986, The Journal of clinical investigation.

[20]  David C. Lee,et al.  Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-alpha. , 2001, Gastroenterology.

[21]  P. Ravdin,et al.  The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers--a review. , 1995, Gene.

[22]  Gideon A. Rodan,et al.  Control of osteoblast function and regulation of bone mass , 2003, Nature.

[23]  David C. Lee,et al.  Amphiregulin Is a Novel Growth Factor Involved in Normal Bone Development and in the Cellular Response to Parathyroid Hormone Stimulation* , 2005, Journal of Biological Chemistry.

[24]  Hiroaki Yamamoto,et al.  Epidermal Growth Factor Receptor-deficient Mice Have Delayed Primary Endochondral Ossification Because of Defective Osteoclast Recruitment* , 2004, Journal of Biological Chemistry.

[25]  E. Wolf,et al.  The epidermal growth factor receptor ligands at a glance , 2009, Journal of cellular physiology.

[26]  J. Hayman,et al.  Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. , 1991, Cancer research.

[27]  I. Fidler,et al.  Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[28]  P. Leder,et al.  Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene , 1988, Cell.

[29]  F. Leenders,et al.  Mammary gland specific hEGF receptor transgene expression induces neoplasia and inhibits differentiation , 2000, Oncogene.

[30]  T. Guise.  Breaking down bone: new insight into site-specific mechanisms of breast cancer osteolysis mediated by metalloproteinases. , 2009, Genes & development.

[31]  Jerry M Maniate,et al.  Targeting the EGFR pathway for cancer therapy. , 2006, Current medicinal chemistry.

[32]  Adriano Angelucci,et al.  Suppression of EGF-R signaling reduces the incidence of prostate cancer metastasis in nude mice. , 2006, Endocrine-related cancer.

[33]  Antony W Burgess,et al.  Epidermal growth factor receptor: mechanisms of activation and signalling. , 2003, Experimental cell research.

[34]  S. Rabbani,et al.  Effect of Herceptin on the development and progression of skeletal metastases in a xenograft model of human breast cancer , 2005, Oncogene.

[35]  Y. Kaneda,et al.  Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities , 2003, The Journal of cell biology.

[36]  I. Fidler,et al.  Blockade of epidermal growth factor receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice. , 2003, Cancer research.

[37]  Xin Lu,et al.  Organotropism of Breast Cancer Metastasis , 2007, Journal of Mammary Gland Biology and Neoplasia.

[38]  G. Mundy.  Metastasis: Metastasis to bone: causes, consequences and therapeutic opportunities , 2002, Nature Reviews Cancer.

[39]  R. Wong,et al.  Expression of Epidermal Growth Factor in Transgenic Mice Causes Growth Retardation* , 2000, The Journal of Biological Chemistry.