Abstract
BackgroundInterleukin-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.MethodologyWe 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.Principal FindingsSerum 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-α production and low RANKL levels, which synergize in promoting osteoclastogenesis.ConclusionsWe 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.
Highlights
Interleukin-7 (IL-7) is a pleiotropic immune regulatory protein predominantly produced by stromal cells and by cells at the inflammatory sites [1]
We showed that IL-7 levels were significantly higher in cancer patients’ co-coltures of both monocytes plus T or B cells than in healthy controls (p,0,0006) and remained nearly steady between day 5 and 10
Our study focused on IL-7 involvement in the spontaneous osteoclastogenesis occurring in cancer patients with osteolytic metastasis
Summary
Interleukin-7 (IL-7) is a pleiotropic immune regulatory protein predominantly produced by stromal cells and by cells at the inflammatory sites [1]. The production of IL7 by some human solid tumors suggests its potential impact on the process of tumorigenesis [3,4], but it is unclear how IL-7 is involved in solid tumor development and progression. Some human solid tumors produce high IL-7 levels, suggesting a potential IL-7 role on tumor development and progression. 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
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