title: Bone metastases in gastric cancer follow a RANKL-independent mechanism.
abstract: Gastric cancer is one of the most common and lethal malignancies worldwide.             Bone metastases in gastric cancer are less common than in other solid tumors,             but when they occur the prognosis is generally poor. Increased osteoclastogenesis             and osteoclast activity are common features in bone metastases caused by different             osteotropic cancer. We investigated osteoclastogenesis and its mechanisms in gastric             cancer by enrolling 31 newly diagnosed gastric cancer patients and 45 healthy             controls. We studied in vitro osteoclastogenesis in the peripheral blood mononuclear             cell cultures of patients and controls, showing spontaneous osteoclastogenesis             for half of the patients. This osteoclastogenesis was RANKL- and TNF-α-independent.             We analyzed primary tumor and bone metastatic tissues of gastric cancer for the             expression of genes involved in osteoclastogenesis. The expression of transforming             growth factor-β (TGF-β), osteoprotegerin (OPG), IL-7 and dickkopf-1 (DKK-1) was             higher in primary tumors than in bone metastases. RANKL was not detectable in             primary tumor or in bone metastatic tissue. The serum RANKL level was significantly             higher in healthy controls than in patients, and it was not related to osteoclastogenesis,             thereby suggesting that RANKL is not involved in the bone metastatic mechanisms             in gastric cancer. We hypothesized a role of RANKL in angiogenesis, thus we compared             the serum levels of RANKL to those of VEGF, since VEGF is directly related to             angiogenesis. Different from RANKL, the VEGF serum levels were higher in gastric             patients than in controls, suggesting a block of the angiogenesis inhibition due             to RANKL. RANKL and VEGF serum levels were not predictive of overall survival             in our cohort of gastric patients.
authors: CeRMS (Center for Experimental Research and Medical Studies), Department of Medical Oncology, San Giovanni Battista Hospital, and Department of Surgical and Medical Discplines, University of Turin, Turin, Italy.
authors: Lucia
authors: L
authors: D'Amico
authors: Maria Antonietta
authors: MA
authors: Satolli
authors: Caterina
authors: C
authors: Mecca
authors: Anna
authors: A
authors: Castiglione
authors: Manuela
authors: M
authors: Ceccarelli
authors: Patrizia
authors: P
authors: D'Amelio
authors: Mauro
authors: M
authors: Garino
authors: Maurizio
authors: M
authors: De Giuli
authors: Sergio
authors: S
authors: Sandrucci
authors: Riccardo
authors: R
authors: Ferracini
authors: Ilaria
authors: I
authors: Roato
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000097:blood* / Q000473:pathology / Q000556:secondary*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008233:Lymphotoxin-alpha / Q000097:blood; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood; D053245:RANK Ligand / Q000097:blood*; D013274:Stomach Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D015851:Interleukin-7; D008233:Lymphotoxin-alpha; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A