title: Wnt signaling pathway inhibitors as promising diagnostic serum markers of osteolytic bone metastasis.
abstract: Despite the clinical importance of bone metastases, we still know little about their onset and progression and current diagnostic tools lack the sensitivity and specificity required for clear early diagnosis. We therefore need to continue studying the pathogenesis of bone metastatic invasion in order to improve diagnosis. The Wnt pathway has been described as having an important role in bone carcinogenesis and metastatic progression. This study investigated the diagnostic potential of the two main Wnt inhibitors, sclerostin and DKK-1, to improve the detection of osteolytic bone metastases. We measured sclerostin and DKK-1, MMP-2 and MMP-9, the bone resorption marker TRAP5b and the metastatic marker survivin in a control group of healthy patients, in patients with primary tumors and in a group with metastasis. Sclerostin and DKK-1 were clearly high in primary tumor patients and even higher in metastatic patients, compared to controls. The close correlations with metastatic markers and bone resorption markers make sclerostin and DKK-1 promising as new biomarkers in the diagnosis of bone osteolytic metastases.
authors.affiliation: IRCCS Galeazzi Orthopedic Institute, Milan, Italy; Department of Biomedical, Surgical and Oral Science, University of Milan, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Galliera
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Marazzi
authors.affiliation: IRCCS Galeazzi Orthopedic Institute, Milan, Italy; Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Drago
authors.affiliation: IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Banfi
authors.affiliation: IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Luzzati
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; U.O.C SMEL-1 Patologia Clinica IRCCS Policlinico San Donato, San Donato (Milan) Italy.
authors.forename: M M
authors.initials: MM
authors.lastname: Corsi Romanelli
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood / Q000556:secondary*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010014:Osteolysis; D011506:Proteins / Q000032:analysis*; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C013247:sclerotin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9