title: Tumor-stromal interactions of the bone microenvironment: in vitro findings and potential in vivo relevance in metastatic lung cancer models.
abstract: Lung cancer comprises a large variety of histological subtypes with a frequent proclivity to form bone metastasis; a condition associated with dismal prognosis. To identify common mechanisms in the development of osteolytic metastasis, we systematically screened a battery of lung cancer cell lines and developed three models of non-small cell lung cancer (NSCLC) with a common proclivity to form osseous lesions, which represented different histological subtypes. Comparative analysis revealed different incidences and latency times. These differences were correlated with cell-type-specific secretion of osteoclastogenic factors, including macrophage inflammatory protein-1α, interleukin-8 and parathyroid hormone-related protein, some of which were exacerbated in conditions that mimicked tumor-stroma interactions. In addition, a distinct signature of matrix metalloproteinase (MMP) activity derived from reciprocal tumor-stroma interactions was detected for each tumor cell line. Thus, these results suggest subtle differences in the mechanisms of bone colonization for each lung cancer subtype, but share, although each to a different degree, dual MMP and osteoclastogenic activities that are differentially enhanced upon tumor-stromal interactions.
authors.affiliation: Division of Oncology, Adhesion and Metastasis Laboratory, Center for Applied Medical Research, University of Navarra, 31080 Pamplona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Luis-Ravelo
authors.forename: Iker
authors.initials: I
authors.lastname: Antón
authors.forename: Silvestre
authors.initials: S
authors.lastname: Vicent
authors.forename: Igor
authors.initials: I
authors.lastname: Hernández
authors.forename: Karmele
authors.initials: K
authors.lastname: Valencia
authors.forename: Carolina
authors.initials: C
authors.lastname: Zandueta
authors.forename: Susana
authors.initials: S
authors.lastname: Martínez-Canarias
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gúrpide
authors.forename: Fernando
authors.initials: F
authors.lastname: Lecanda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D012333:RNA, Messenger; D020782:Matrix Metalloproteinases