Secretory leukocyte protease inhibitor modulates urethane-induced lung carcinogenesis

Cezary Jan treda, Tatsuro Fukuhara, Takuji Suzuki, Akira Nakamura, Jamal Zaini, Toshiaki Kikuchi, Masahito Ebina, Toshihiro Nukiwa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Secretory leukocyte protease inhibitor (SLPI), 11.7 kDa serine protease inhibitor, is produced primarily in the respiratory tract, but it is often elevated in lung, head/neck and ovarian cancers. SLPI expression in relation to cancer progression, metastasis and invasion has been studied extensively in non-small cell lung cancer. However, the role of SLPI during the early stages of carcinogenesis remains unknown. We hypothesized that SLPI is required from the initiation and promotion to the progression of lung carcinogenesis. A skin allograft model using SLPI-knockout (SLPI-KO) mice and short hairpin RNA-treated cells was used to demonstrate that SLPI expression in tumor cells is crucial for tumor formation. Moreover, lung tumorigenesis induced by urethane, a chemical lung carcinogen, was significantly suppressed in SLPI-KO mice in association with decreased nuclear factor-κB (NF-κB) activity. SLPI deficiency also resulted in decreased cell numbers and decreased production of inflammatory cytokines in bronchoalveolar lavage fluids. The suppression of NF-κB activation in SLPI-KO mice was associated with lower expression of NF-κB-related survival genes and DNA repair genes. Our findings demonstrate that SLPI plays an important role from the initial stages of lung carcinogenesis to the progression of lung cancer in an NF-κB-dependent manner.

Original languageEnglish
Pages (from-to)896-904
Number of pages9
JournalCarcinogenesis
Volume35
Issue number4
DOIs
Publication statusPublished - 1 Jan 2014

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