title: Low Molecular Weight Protein Tyrosine Phosphatase Slow Isoform Knockdown in MDA-MB-435 Cells Decreases RAW 264.7 Osteoclastic Differentiation.
abstract: OBJECTIVE
  During the bone metastatic process, tumor cells and bone cells drive a vicious cycle stimulating growth and activity of each other. We here address how low molecular weight protein tyrosine phosphatase (LMW-PTP) could be involved in this process.
  
  
  METHODS
  We targeted LMW-PTP by siRNA and evaluated the effect of various soluble factors released to the culture medium by the MDA-MB-435 breast cancer cell line, in RAW 264.7 osteoclastogenesis.
  
  
  RESULTS
  We showed that these soluble factors did not change RAW 264.7 osteoclastogenic potential. The knockdown of the LMW-PTP slow isoform decreased osteoclastogenesis of RAW 264.7, showing less active Src. The knockdown of LMW-PTP and its slow isoform decreased the release of IL-8 but not IL-6 in MDA-MB-435.
  
  
  CONCLUSIONS
  The LMW-PTP slow isoform can be an important protein in bone metastatic disease, with a fundamental role in the interplay between tumor cells and osteoclasts, through the regulation of Src activity and IL-8 secretion.
authors.affiliation: Genetics Laboratory, Environmental Health Institute (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Irina
authors.initials: I
authors.lastname: Alho
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal Serviço de Oncologia Médica, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte, Lisbon, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
authors.affiliation: Genetics Laboratory, Environmental Health Institute (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal Instituto Rocha Cabral Lisboa, Lisbon, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Bicho
authors.affiliation: Genetics Laboratory, Environmental Health Institute (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal constancacoelho@medicina.ulisboa.pt.
authors.forename: Constança
authors.initials: C
authors.lastname: Coelho
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000818:Animals; D001859:Bone Neoplasms; D001943:Breast Neoplasms / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; D034741:RNA, Small Interfering; C505688:TNFSF11 protein, human; D019000:Phosphotyrosine; D019061:src-Family Kinases; C490428:Acp1 protein, mouse; D017027:Protein Tyrosine Phosphatases
keywords: Bone metastases; IL-8; LMW-PTP; Src; slow isoform