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Interleukin-37 suppresses tumor growth through inhibition of angiogenesis in non-small cell lung cancer
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نویسنده
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ge g. ,wang a. ,yang j. ,chen y. ,yang j. ,li y. ,xue y.
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منبع
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journal of experimental and clinical cancer research - 2016 - دوره : 35 - شماره : 1
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چکیده
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Background: interleukin-37 (il-37),a newly identified member of the il-1 family,has been known to play an immunosuppressive role in a variety of inflammatory disorders,but whether it participates in the regulation of pathogenesis of non-small cell lung cancer (nsclc) has not been investigated. methods: real-time polymerase chain reaction (pcr),western blotting,and immunohistochemical staining were employed to detect il-37 expression in nsclc tissues and corresponding adjacent tissues. the correlations between il-37 expression and clinicopathological characteristics,prognosis were analyzed. stable clone with overexpression of il-37 was generated in h1299 cell lines. cell growth,cell cycle and cell apoptosis assays were carried out for detecting proliferation and apoptosis of h1299 cells. the effects of il-37 on nsclc progression in vivo was performed in a xenografted lung tumor model in nude mice. the concentrations of il-37 and vegf in the s growth medium supernatants were quantified by elisa. the antiangiogenic effect of il-37 on huvec was measured by tube formation assay. results: il-37 mrna and protein expressions were significantly decreased in nsclc tissues,and decreased intratumoral il-37 expression was significantly associated with tumor state,tnm stage and poor prognosis in nsclc patients. in addition,intratumoral il-37 expression was an independent prognostic factors for overall survival (hazard ratio=2.047; p=0.011). overexpression of il-37 exerted no direct effect on cell proliferation and apoptosis of h1299 lung cancer cells in vitro,but significantly inhibited tumor growth in a h1299 xenograft model in vivo. furthermore,there was no significant change in immune cell infiltration in il-37 over-expressing tumors; instead,we found decreased microvessel density (mvd) and vegf levels in il-37-expressing tumors. additional studies showed il-37 could directly inhibit huvec cells growth and capillary structure formation. finally,we found that decreased il-37 expression was associated with high mvd in nsclc patients. conclusions: our findings demonstrate a protective role for il-37 in lung cancer development,possibly through inhibiting tumor angiogenesis. il-37 could serve as a promising therapeutic target for nsclc. © 2016 ge et al.
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کلیدواژه
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Interleukin-37; Microvessel density; Non-small cell lung cancer; Tumor angiogenesis
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آدرس
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department of surgical oncology,first affiliated hospital of xi'an jiaotong university,277 yantaxi road,xi'an,shaanxi 710061, China, department of neurosurgery,ninth hospital of xian,xi'an,710054, China, department of oncology,xijing hospital,fourth military medical university,no.15 changle west road,xi'an,shannxi 710032, China, department of oncology,xijing hospital,fourth military medical university,no.15 changle west road,xi'an,shannxi 710032, China, department of oncology,xijing hospital,fourth military medical university,no.15 changle west road,xi'an,shannxi 710032, China, department of oncology,xijing hospital,fourth military medical university,no.15 changle west road,xi'an,shannxi 710032, China, department of oncology,xijing hospital,fourth military medical university,no.15 changle west road,xi'an,shannxi 710032, China
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