1. Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad
- Author
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John Foley, Jennifer L. Gilmore, Nicole K. Nickerson, Theresa A. Guise, Angela Bruzzaniti, Erin Crismore, and Khalid S. Mohammad
- Subjects
Anatomy and Physiology ,lcsh:Medicine ,Fat pad ,Mice ,Osteogenesis ,Molecular Cell Biology ,Basic Cancer Research ,Epidermal growth factor receptor ,Phosphorylation ,RNA, Small Interfering ,skin and connective tissue diseases ,lcsh:Science ,Musculoskeletal System ,Multidisciplinary ,biology ,Obstetrics and Gynecology ,Metastatic breast cancer ,ErbB Receptors ,Oncology ,Intercellular Signaling Peptides and Proteins ,Medicine ,Female ,Signal Transduction ,Research Article ,medicine.medical_specialty ,EGF Family of Proteins ,Mice, Nude ,Breast Neoplasms ,Amphiregulin ,Bone and Bones ,Paracrine signalling ,Breast cancer ,Mammary Glands, Animal ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Autocrine signalling ,Biology ,Glycoproteins ,lcsh:R ,Cancer ,Cancers and Neoplasms ,X-Ray Microtomography ,medicine.disease ,Endocrinology ,Cancer research ,biology.protein ,lcsh:Q - Abstract
Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p
- Published
- 2012