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.