ArticlePloS one2012
Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
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- Leveraging Bulk and Single-Cell RNA Sequencing Data of NSCLC Tumor Microenvironment and Therapeutic Potential of NLOC-15A, A Novel Multi-Target Small Molecule.Frontiers in immunology · 2022Article
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- Parathyroid hormone-like hormone plays a dual role in neuroblastoma depending on PTH1R expression.Molecular oncology · 2019Article
- Counting growth factors in single cells with infrared quantum dots to measure discrete stimulation distributions.Nature communications · 2019Article
- CAPE-Frontiers in oncology · 2019Article
- Metastatic and triple-negative breast cancer: challenges and treatment options.Drug delivery and translational research · 2018Review
- The role of AP-1 in self-sufficient proliferation and migration of cancer cells and its potential impact on an autocrine/paracrine loop.Oncotarget · 2018Article
- hsa-miR-135a-1 inhibits prostate cancer cell growth and migration by targeting EGFR.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- The role of tumour-associated macrophages in bone metastasis.Journal of bone oncology · 2016Article
- Golgi phosphoprotein 3 regulates metastasis of prostate cancer via matrix metalloproteinase 9.International journal of clinical and experimental pathology · 2015Article
- SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma.International journal of breast cancer · 2015Article
- Brefeldin A reduces anchorage-independent survival, cancer stem cell potential and migration of MDA-MB-231 human breast cancer cells.Molecules (Basel, Switzerland) · 2014Article
- Plakophilin-2 promotes tumor development by enhancing ligand-dependent and -independent epidermal growth factor receptor dimerization and activation.Molecular and cellular biology · 2014Article
- Homozygous truncating PTPRF mutation causes athelia.Human genetics · 2014Article
- Nuclear localization of Kaiso promotes the poorly differentiated phenotype and EMT in infiltrating ductal carcinomas.Clinical & experimental metastasis · 2014Article
- Metastasis of Breast Tumor Cells to Brain Is Suppressed by Phenethyl Isothiocyanate in a Novel In Vivo Metastasis Model.PloS one · 2013Article
- Autocrine-derived epidermal growth factor receptor ligands contribute to recruitment of tumor-associated macrophage and growth of basal breast cancer cells in vivo.Oncology research · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland.
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Registered trials
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