title: IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor.
abstract: BACKGROUND
  Interleukin-7 (IL-7) is a potent regulator of lymphocyte development, which has also significant effects on bone; in fact it is a potent osteoclastogenic factor. Some human solid tumors produce high IL-7 levels, suggesting a potential IL-7 role on tumor development and progression.
  
  
  METHODS
  We studied 50 male patients affected by solid tumors, and their blood samples were collected at tumor diagnosis. PBMCs were isolated and cultured with/without IL-7 to study its influence on osteoclastogenesis. Serum and cell culture supernatant IL-7 levels were measured by ELISA. The quantitative analysis of IL-7 expression on T and B cells was performed by Real-Time PCR.
  
  
  RESULTS
  Serum IL-7 levels were highest in osteolytic cancer patients, followed by cancer patients without bone lesions, and then healthy controls. We showed the IL-7 production in PBMC cultures and particularly in monocyte and B cell co-cultures. A quantitative analysis of IL-7 expression in T and B cells confirmed that B cells had a high IL-7 expression. In all cell culture conditions, IL-7 significantly increased osteoclastogenesis and an anti-IL-7 antibody inhibited it. We demonstrated that IL-7 supports OC formation by inducing the TNF-alpha production and low RANKL levels, which synergize in promoting osteoclastogenesis.
  
  
  CONCLUSIONS
  We demonstrated the presence of high serum IL-7 levels in patients with bone metastasis, suggesting the use of serum IL-7 level as a clinical marker of disease progression and of bone involvement. Moreover, we showed the capability of IL-7 to stimulate spontaneous osteoclastogenesis of bone metastatic patients and to induce osteoclastogenesis in cancer patients without bone involvement. These findings add further details to the disclosure of the mechanisms controlling bone metastasis in solid tumors.
authors.affiliation: Center for Experimental Research and Medical Studies (CeRMS), University and AZO San Giovanni Battista, Turin, Italy; Department of Medical Oncology, University and AZO San Giovanni Battista, Turin, Italy. roato78@libero.it
authors.forename: Ilaria
authors.initials: I
authors.lastname: Roato
authors.forename: Giacomina
authors.initials: G
authors.lastname: Brunetti
authors.forename: Eva
authors.initials: E
authors.lastname: Gorassini
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonello
authors.forename: Lucio
authors.initials: L
authors.lastname: Buffoni
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredi
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
authors.forename: Davide
authors.initials: D
authors.lastname: Ottaviani
authors.forename: Libero
authors.initials: L
authors.lastname: Ciuffreda
authors.forename: Antonio
authors.initials: A
authors.lastname: Mussa
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ferracini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000502:physiology; D001859:Bone Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary; D001862:Bone Resorption / Q000097:blood / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D015851:Interleukin-7 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology*; D053245:RANK Ligand / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: C508605:IL7 protein, human; D015851:Interleukin-7; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha