3574

IL7

interleukin 7;IL7;interleukin 7

interleukin-7

8q12-q13

protein-coding

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. METHODOLOGY: 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. PRINCIPAL FINDINGS: 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.

BACKGROUND AND OBJECTIVE: it has been proven that lymph node metastasis was closely related to prognosis of lung cancer. Interleukin-7 (IL-7) and interleukin-7 receptor (IL-7R) could promote lymph node metastasis through vascular endothelial growth factor-D (VEGF-D). The aim of this study is to explore the expressions of IL-7 and IL-7R in lung cancer and the relationship between them with lymph node metastasis and prognosis in non-small cell lung cancer (NSCLC). METHODS: the expressions of IL-7 and IL-7R in 95 cases of NSCLC were detected with immunohistochemistry method and the relationship between IL-7 and IL-7R and their impact on lung cancer patients' outcomes were analyzed. RESULTS: in 95 cases of NSCLC, the high expression rates of IL-7, IL-7R and VEGF-D were 63.16%, 61.05% and 58.95%. The expressions of IL-7 and IL-7R were correlated closely with clinic stage and lymph node metastasis, but had no relationship with age, gender, histological type and differentiation degree. The lymphatic vessel density (LVD) mean of the group with high expressions of IL-7 and IL-7R was higher than that with low or negative expressions of IL-7 and IL-7R, and they were significant different in statistics. Log-rank analysis showed that the postoperative survival period was significantly shorter in high expression groups IL-7, IL-7R and VEGF-D comparing with that in low or negative groups. CONCLUSIONS: the high expression of IL-7 and IL-7R is highly positie correlated with clinic stage, lymph node metastasis, VEGF-D, LVD and poor prognosis in Non-small cell lung cancer.