Hepatocyte growth factor enhances CXCR4 expression favoring breast cancer cell invasiveness.
Microenvironmental factors affect different aspects of tumor cell biology, including cell survival, invasion, and metastasis. Here, we report that hepatocyte growth factor and hypoxia may contribute to breast carcinoma cell invasiveness by inducing the chemokine receptor CXCR4. Hepatocyte growth factor enhanced CXCR4 mRNA and protein expression exclusively in MCF-7 (low invasive) carcinoma cells, while in response to hypoxia, CXCR4 induction was observed in both MCF-7 and MDA-MB 231 (highly invasive) carcinoma cells. The receptor induction had a functional role in cancer cells, as demonstrated by the fact that hepatocyte growth factor pretreatment promoted MCF-7 cell migration toward the CXCR4-specific ligand CXCL12. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) and phosphoinositide-3-kinase (PI3K) transduction pathways seemed to be differently implicated in the early induction of CXCR4 by hepatocyte growth factor or hypoxia in the two breast carcinoma cells examined.
Matteucci
Emanuela
E
Institute of General Pathology, School of Medicine, University of Milan, via Luigi Mangiagalli, 31-20133 Milan, Italy.
Locati
Massimo
M
Desiderio
Maria Alfonsina
MA
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011498:Protein Precursors; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases