title: The β 2-Adrenergic Agonist Salbutamol Inhibits Migration, Invasion and Metastasis of the Human Breast Cancer MDA-MB- 231 Cell Line.
abstract: BACKGROUND
  Breast cancer is the most diagnosed and the major cause of cancer death in women worldwide. Metastasis is the main cause of these deaths. The metastatic cascade involves multiple steps and it has been described that adrenergic receptors can modulate this process at multiple levels. However, β -adrenergic action in breast cancer is controversial. We have previously shown that β-adrenergic agonists inhibit cell proliferation and tumor growth of numerous breast cancer models.
  
  
  OBJECTIVE
  The purpose of the present investigation was to evaluate adrenergic effect in parameters related to tumor progression (migration, invasion and metastases) in two human breast cancer cell lines.
  
  
  METHODS
  Migration was assessed in IBH-6 and MDA-MB-231 cells by time-lapse videomicroscopy and modified Boyden chambers. Invasion was evaluated by Transwells coated with Matrigel and expression of pro-metastatic genes was determined by RT-qPCR. Experimental metastases studies were performed by injection of the cells in the tail vein of NSG immuno-deficient mice.
  
  
  RESULTS
  In both cell lines, salbutamol (β2-agonist) and propranolol (β-blocker) significantly diminished cell migration while epinephrine exerted opposite effects. Moreover, salbutamol inhibited invasion of both breast cancer cell lines and enhanced adhesion to extracellular matrix. Salbutamol treatment was also able to decrease the expression of pro-metastatic genes in MDA-MB-231 cells. Finally, this compound decreased the number and size of MDA-MB-231 lung experimental metastases in NSG immuno- deficient mice. No effect on the establishment of IBH-6 metastases was observed.
  
  
  CONCLUSIONS
  Our results suggest that salbutamol could be an effective adjuvant drug for the treatment of metastatic breast cancer.
authors.affiliation: Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires. Argentina.
authors.forename: Ezequiel Mariano
authors.initials: EM
authors.lastname: Rivero
authors.affiliation: Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires. Argentina.
authors.forename: Cecilia Pérez
authors.initials: CP
authors.lastname: Piñero
authors.affiliation: Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires. Argentina.
authors.forename: Lucía
authors.initials: L
authors.lastname: Gargiulo
authors.affiliation: Institute for Immunology, ZBAF, Witten/Herdecke University, Witten. Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Entschladen
authors.affiliation: Institute for Immunology, ZBAF, Witten/Herdecke University, Witten. Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zänker
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca INIBIBB- CONICET. Bahía Blanca. Argentina.
authors.forename: Ariana
authors.initials: A
authors.lastname: Bruzzone
authors.affiliation: Instituto de Biología y Medicina Experimental, IBYME-CONICET, Buenos Aires. Argentina.
authors.forename: Isabel Alicia
authors.initials: IA
authors.lastname: Lüthy
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D011433:Propranolol / Q000494:pharmacology; D011509:Proteoglycans / Q000494:pharmacology
chemical_list: D000322:Adrenergic Agonists; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D011433:Propranolol; D000420:Albuterol
keywords: Breast cancer; IBH-6; MDA-MB-231; metastasis; salbutamol; β-adrenoceptors