Bone metastases in gastric cancer follow a RANKL-independent mechanism

D'Amico,Lucia; Satolli,Maria  Antonietta; Mecca,Caterina; Castiglione,Anna; Ceccarelli,Manuela; D'Amelio,Patrizia; Garino,Mauro; De Giuli,Maurizio; Sandrucci,Sergio; Ferracini,Riccardo; Roato,Ilaria

doi:10.3892/or.2013.2280

Bone metastases in gastric cancer follow a RANKL-independent mechanism

Authors:
- Lucia D'Amico
- Maria Antonietta Satolli
- Caterina Mecca
- Anna Castiglione
- Manuela Ceccarelli
- Patrizia D'Amelio
- Mauro Garino
- Maurizio De Giuli
- Sergio Sandrucci
- Riccardo Ferracini
- Ilaria Roato
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Affiliations: CeRMS (Center for Experimental Research and Medical Studies), San Giovanni Battista Hospital, Turin, Italy, Department of Medical Oncology, San Giovanni Battista Hospital, Turin, Italy, Unit of Cancer Epidemiology, San Giovanni Battista Hospital, Turin, Italy, Department of Surgical and Medical Disciplines, University of Turin, Turin, Italy, Department of Surgery, San Giovanni Battista Hospital and University of Turin, Turin, Italy, Department of Oncologic Surgery, San Giovanni Battista Hospital, Turin, Italy, Department of Orthopaedics, San Giovanni Battista Hospital, Turin, Italy
Published online on: February 6, 2013 https://doi.org/10.3892/or.2013.2280
Pages: 1453-1458

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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.

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