title: Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis.
abstract: Chronic inflammation plays important roles at different stages of cancer development, including carcinogenesis, tumor invasion, and metastasis, but molecular mechanisms linking inflammation to cancer development have not been fully clarified. Here, we report that expression of angiopoietin-like protein 2 (Angptl2), recently identified as a chronic inflammation mediator, is highly correlated with the frequency of carcinogenesis in a chemically induced skin squamous cell carcinoma (SCC) mouse model. Furthermore, Angptl2 expression in SCC is highly correlated with the frequency of tumor cell metastasis to distant secondary organs and lymph nodes. When SCC was induced in transgenic mice expressing Angptl2 in skin epithelial cells, epithelial-to-mesenchymal transitions in SCC as well as tumor angiogenesis and lymphangiogenesis were significantly increased, resulting in increased tumor cell metastasis and shortened survival compared with wild-type mice. Conversely, in a chemically induced SCC mouse model, carcinogenesis and metastasis were markedly attenuated in Angptl2 knockout mice, resulting in extended survival compared with wild-type mice. Overall, we propose that Angptl2 contributes to increased carcinogenesis and metastasis and represents a novel target to antagonize these pathologies.
authors: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Jun
authors: J
authors: Aoi
authors: Motoyoshi
authors: M
authors: Endo
authors: Tsuyoshi
authors: T
authors: Kadomatsu
authors: Keishi
authors: K
authors: Miyata
authors: Masahiro
authors: M
authors: Nakano
authors: Haruki
authors: H
authors: Horiguchi
authors: Aki
authors: A
authors: Ogata
authors: Haruki
authors: H
authors: Odagiri
authors: Masato
authors: M
authors: Yano
authors: Kimi
authors: K
authors: Araki
authors: Masatoshi
authors: M
authors: Jinnin
authors: Takaaki
authors: T
authors: Ito
authors: Satoshi
authors: S
authors: Hirakawa
authors: Hironobu
authors: H
authors: Ihn
authors: Yuichi
authors: Y
authors: Oike
mesh_terms: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015151:Immunoblotting; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D042583:Lymphangiogenesis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D002273:Carcinogens; D018836:Inflammation Mediators; D013755:Tetradecanoylphorbol Acetate