Spontaneous osteoclastogenesis is a predictive factor for bone metastases from non-small cell lung cancer

Roato, Ilaria; Gorassini, Eva; Buffoni, L; Lybéris, Paraskevas; Ruffini, Enrico; Bonello, Lisa; Baldi, Ileana; Ciuffreda, Libero; Mussa, Antonio; Ferracini, Riccardo

doi:10.1016/j.lungcan.2007.10.016

Cited by 29 publications

(47 citation statements)

References 13 publications

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“…These cells derive from the fusion of marrowderived mononuclear phagocytes circulating in peripheral blood (Massey and Flanagan 1999). It has been demonstrated previously that pathological resorption is due, at least in part, to an increased number of OC precursors in certain situations (Li et al 2004;Roato et al 2007). Increased spontaneous osteoclastogenesis has recently been reported in 18 women affected by postmenopausal osteoporosis, and suggested as one of the determinants of the bone loss, as directly related to diminished bone density (D_Amelio et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…From each patient and control, the circulating mononuclear cells were obtained from peripheral blood samples according to the Ficoll method, as previously described (Roato et al 2007). All the cell incubations were performed in triplicate in 96-well plates using aminimal essential medium (a-MEM, supplied Invitrogen, Carlsbad, CA, USA), supplemented with 10% fetal bovine serum, benzylpenicillin (100 IU/ml), and streptomycin (100 mg/ml) (supplied by Lonza, Basel, Switzerland), and maintained at 37-C in a humidified atmosphere of 5% CO 2 .…”

Section: Cell Isolation and Culturesmentioning

confidence: 99%

“…Since some diseases characterized by bone loss have been related to increased OC activity (Roato et al 2007), we hypothesized that these cells could play a role in bone impairment of PKU. As the presence of an OC precursor from peripheral blood mononuclear cells (PBMCs) and its possible maturation in vitro has been demonstrated (D_Amelio et al 2005;Roato et al 2007), we investigated the spontaneous osteoclastogenesis in PKU patients compared with that observed in healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Porta

Roato²,

Mussa

et al. 2008

J of Inher Metab Disea

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Phenylketonuria (PKU) is commonly complicated by a progressive bone impairment of uncertain aetiology. The therapeutic phenylalanine (Phe)-restricted diet and the possible noxious effects of high plasma Phe concentrations on bone have previously been suggested as possible determinant factors. Since osteoclasts are involved in bone reabsorption, they could play a role in determining bone damage in PKU. The reported increased excretion of bone resorption markers in PKU patients is consistent with this hypothesis. Although different diseases characterized by bone loss have been related to increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells (PBMCs), to date there is no evidence of increased osteoclast formation in PKU. In this study, we compared the spontaneous osteoclastogenesis from PBMCs in 20 patients affected by PKU with that observed in age- and sex-matched healthy subjects. Phenylketonuric patients showed the number of osteoclasts to be almost double that observed in controls (159.9 ± 79.5 and 87.8 ± 44.7, respectively; p = 0.001). Moreover, a strict direct correlation between the spontaneous osteoclastogenesis in PKU patients and the mean blood Phe concentrations in the preceding year was observed (r = 0.576; p = 0.010). An imbalance between bone formation and bone resorption might explain, at least in part, the pathogenesis of bone loss in this disease. These findings could provide new insights into the biological mechanisms underlying bone damage in PKU.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Isolation and Culturesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Porta

Roato²,

Mussa

et al. 2008

J of Inher Metab Disea

Self Cite

View full text Add to dashboard Cite

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“…Spontaneous osteoclastogenesis was observed in half of the patients. Moreover, unlike other osteotropic solid tumors such as breast and lung cancer (19,24,25), in gastric cancer the osteoclastogenesis was independent of RANKL and TNF-α. We consider that other molecules could be involved in the stimulation of osteoclasto genesis, such as IL-11, which has been reported to support human osteoclastogenesis with IL-6 by a RANKLindependent mechanism (26).…”

Section: Discussionmentioning

confidence: 88%

Bone metastases in gastric cancer follow a RANKL-independent mechanism

et al. 2013

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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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“…This has been documented in patients with metastatic neuroblastoma and poor responders to chemotherapy (56), in nonsmall cell lung cancer, where spontaneous increase in osteoclastogenesis from peripheral blood mononuclear cells, higher serum interleukin-7 levels and urinary crosslinks were observed in patients with bone metastases (57), or in patients with bone met~tases from prostate carcinoma, which showed an enhanced osteoclastogenesis, and increased Dkk-l serum levelst issue gene expression (58).…”

Section: Bone Tumoursmentioning

confidence: 91%

Orthopaedic Research in Italy: State of the Art

Cenni

Scioscia²,

Baldini

2011

Int J Immunopathol Pharmacol

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The most significant results in experimental and clinical orthopaedic research in Italy within the last three years have been primarily in major congenital diseases, bone tumors, regenerative medicine, joint replacements, spine, tendons and ligaments, The data presented in the following discussion is comparable with leading international results, highlighting Italian orthopaedic research excellemce as well as its shortcomings.There has been continued innovation in orthopaedic research over the past years. The advances in basic science, particularly in molecular and cell biology, in material science and in nanotechnology, has provided the tools for bone engineering, bone imaging and innovative methods for diagnosis and treatment of primitive and metastatic bone tumours. At this point, it seems necessary to examine to what extent are the limitations of these new orthopaedic techniques as well as the prevalent topics that should be explored and the position of the Italian orthopedic research on a global stage.

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Spontaneous osteoclastogenesis is a predictive factor for bone metastases from non-small cell lung cancer

Cited by 29 publications

References 13 publications

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria

Bone metastases in gastric cancer follow a RANKL-independent mechanism

Orthopaedic Research in Italy: State of the Art

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