title: Neuropilin-1 is involved in regulation of apoptosis and migration of human colon cancer.
abstract: Vascular endothelial growth factor (VEGF) plays critical roles in cancer aggressiveness. We investigated the clinical and biological significance of neuropilin (NP)-1, a member of the VEGF receptor family, in colon carcinoma. We transfected NP-1-specific small interfering RNA (siRNA) into a human colon adenocarcinoma cell line, WiDR, and investigated its effect on proliferation, migration, and apoptosis. We also examined the relationship between clinicopathologic features and NP-1 expression in 146 patients with advanced colorectal carcinoma who had undergone surgery. Inhibition of NP-1 expression in WiDR cells by RNA interference decreased cell migration (no treatment, 143.3/field; mock, 146.8/field; scrambled siRNA, 134.6/field; NP-1 siRNA 79.6/field) and promoted apoptosis (no treatment, 3.52%; scrambled siRNA, 3.80%; NP-1 siRNA, 14.22%), but did not alter cell proliferation. In patients with advanced colorectal carcinoma, those with tumors with high levels of NP-1 staining showed a significantly higher incidence of lymph node (73.0%) or liver (86.2%) metastasis, greater microvessel density (MVD) (60.4/field), greater number of proliferating carcinoma cells (48.6%), and lesser number of apoptotic carcinoma cells (5.70 per thousand) than those with tumors with low levels of NP-1 staining (lymph node, 56.9%; liver, 59.8%; MVD, 47.8/field; proliferating cells, 42.0%; apoptosis, 8.44 per thousand). Survival for patients with tumors with high levels of NP-1 staining was significantly shorter than for those with tumors with low levels of NP-1 staining. Our results suggest that autocrine-NP-1 pathways control the migration and survival of colon carcinoma cells. NP-1 expression may stimulate tumor growth by enhanced angiogenesis and suppression of tumor cell apoptosis, which lead to metastasis and poor prognosis.
authors.affiliation: Department of Medicine and Molecular Science, Graduated School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ochiumi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitadai
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Morihisa
authors.initials: M
authors.lastname: Akagi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yoshihara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor