Content area
Full Text
Transgenic Res (2010) 19:11091117 DOI 10.1007/s11248-010-9384-7
ORIGINAL PAPER
Chemokine CXCL14/BRAK transgenic mice suppress growth of carcinoma cell xenografts
Kazuhito Izukuri Kenji Suzuki
Nobuyuki Yajima Shigeyuki Ozawa
Shin Ito Eiro Kubota Ryu-Ichiro Hata
Received: 10 November 2009 / Accepted: 8 March 2010 / Published online: 24 March 2010 Springer Science+Business Media B.V. 2010
Abstract We reported previously that the forced expression of the chemokine BRAK, also called CXCL14 in head and neck squamous cell carcinoma (HNSCC) cells decreased the rate of tumor formation and size of tumor xenografts compared with mock-vector treated cells in athymic nude mice or in severe combined immunodeciency mice. This suppression occurred even though the growth rates of these cells were the same under in vitro culture conditions, suggesting that a high expression level of the gene in tumor cells is important for the suppression of tumor establishment in vivo. The aim of this study was to determine whether CXCL14/BRAK transgenic mice show resistance to tumor cell xenografts or not. CXCL14/BRAK cDNA was introduced into male C57BL/6 J pronuclei, and 10 founder transgenic mice (Tg) were obtained. Two lines of mice expressed over
10 times higher CXCL14/BRAK protein levels (14 and 11 ng/ml plasma, respectively) than normal blood level(0.9 ng/ml plasma), without apparent abnormality. The sizes of Lewis lung carcinoma and B16 melanoma cell xenografts in Tg mice were signicantly smaller than those in control wild-type mice, indicating that CXCL14/BRAK, rst found as a suppressor of tumor progression of HNSCC, also suppresses the progression of a carcinoma of other tissue origin. Immunohisto-chemical studies showed that invasion of blood vessels into tumors was suppressed in tumor xenografts of CXCL14/BRAK Tg mice. These results indicate that CXCL14/BRAK suppressed tumor cell xenografts by functioning paracrine or endocrine fashion and that CXCL14/BRAK is a very promising molecular target for tumor suppression without side effects.
Keywords Chemokine CXCL14/BRAK
Tumor suppression Lewis lung carcinoma cells
Transgenic mouse Tumor therapy
Introduction
Tumors develop in multiple steps (Vogelstein et al. 1988; Hanahan and Weinberg 2000; Sidransky 2002), and tumor progression is dependent on the balance of the expression between tumor progression-promoting andsuppressing genes being in favor of the former at each step (Bissell and Radisky 2001; Akhurst 2002; Benatti et al. 2008). In order to nd drugs to prevent
Kazuhito...