title: Netrin-4 overexpression suppresses primary and metastatic colorectal             tumor progression.
abstract: Tumor angiogenesis is closely associated with clinical staging and has been             proposed to correlate with clinical response in terms of subsequent metastases             following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore,             we sought to examine the effects of NT-4 on the primary tumor growth of colon             cancer cells, liver and lung metastases of colon cancer cells, and responses following             primary tumor resection. We used 3 different mouse models of orthotopic primary             tumor and liver and lung metastases, comparing 2 human colon cancer cells lines:             wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells.             NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts             in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; p<0.0001) as well as its related             local and systemic recurrence (38 vs. 0%; p<0.01). NT-4 overexpression also             markedly decreased colorectal cancer progression in terms of tumor number and             volume of liver metastases in the NT-4 group of the orthotopic liver metastasis             model (25 vs. 90% and 4±1 vs. 709±190 mm3, p<0.001 and p<0.05). Collectively,             our findings indicate that NT-4 overexpression decreases colorectal lung metastasis             and its associated lymph node involvement. NT-4 overexpression decreases tumor             recurrence and metastasis after surgical resection, likely via an anti-angiogenic             effect. These observations suggest that NT-4 may hold therapeutic potential in             the treatment of colorectal cancer growth and major metastatic sites.
authors.affiliation: INSERM U965 Angiogenesis and Translational Research, Department of Digestive Diseases, Paris Diderot, Paris 7 University, Lariboisière Hospital, AP-HP, 75010 Paris, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Eveno
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Contreres
authors.forename: Patricia
authors.initials: P
authors.lastname: Hainaud
authors.forename: Judith
authors.initials: J
authors.lastname: Nemeth
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dupuy
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075385:Netrins; D014407:Tumor Cells, Cultured
chemical_list: D009414:Nerve Growth Factors; D000075385:Netrins; C416214:Ntn4 protein, mouse