OBJECTIVE: Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a prognostic indicator of human malignancies according to the tumor type in which it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal experimental model, and also how it could affect tumor angiogenesis and prognosis in NSCLC patients. METHODS AND RESULTS: Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells, but decreased tumor growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor (EGFR) family proteins and c-Met in two human lung cancer cell lines in vitro. However, cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8. Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis. Using immunohistochemistry, we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell carcinoma (p=0.034), the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive. CONCLUSION: Therefore, the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC.
OBJECTIVE: Expression of N-myc downstream-regulated gene 1 (NDRG1)/Cap43 is a prognostic indicator of humanmalignancies according to the tumor type in which it occurs. We investigated how NDRG1/Cap43 could affect tumor growth and angiogenesis in non-small-cell lung cancer (NSCLC) in vivo using an animal experimental model, and also how it could affect tumor angiogenesis and prognosis in NSCLCpatients. METHODS AND RESULTS: Knockdown of NDRG1/Cap43 in lung cancer cells using a specific small interfering RNA resulted in growth rates in culture that were similar to those of counterpart control cells, but decreased tumor growth rates in vivo markedly. Stable NDRG1/Cap43 knockdown did not induce consistent changes in the expression of Epidermal growth factor receptor (EGFR) family proteins and c-Met in two humanlung cancer cell lines in vitro. However, cell lines with NDRG1/Cap43 knockdown showed markedly decreased production of the potent angiogenic factors vascular endothelial growth factor-A and interleukin-8. Cells with knockdown of NDRG1/Cap43 showed marked reduction of tumor-induced angiogenesis. Using immunohistochemistry, we examined 182 surgically resected specimens of NSCLC for expression of NDRG1/Cap43 and tumor angiogenesis. High microvessel density in the tumor was significantly associated with nuclear positivity for NDRG1/Cap43 in both adenocarcinoma (p = 0.003) and squamous cell carcinoma (p=0.041). For both adenocarcinoma (p = 0.031) and squamous cell carcinoma (p=0.034), the survival curve of patients negative for nuclear NDRG1/Cap43 expression differed significantly from that of patients who were positive. CONCLUSION: Therefore, the expression of NDRG1/Cap43 may be predictive of tumor angiogenesis and poor prognosis in NSCLC.
Authors: Sabine A S Langie; Gudrun Koppen; Daniel Desaulniers; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Amaya Azqueta; William H Bisson; Dustin G Brown; Gunnar Brunborg; Amelia K Charles; Tao Chen; Annamaria Colacci; Firouz Darroudi; Stefano Forte; Laetitia Gonzalez; Roslida A Hamid; Lisbeth E Knudsen; Luc Leyns; Adela Lopez de Cerain Salsamendi; Lorenzo Memeo; Chiara Mondello; Carmel Mothersill; Ann-Karin Olsen; Sofia Pavanello; Jayadev Raju; Emilio Rojas; Rabindra Roy; Elizabeth P Ryan; Patricia Ostrosky-Wegman; Hosni K Salem; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Frederik J Van Schooten; Mahara Valverde; Jordan Woodrick; Luoping Zhang; Nik van Larebeke; Micheline Kirsch-Volders; Andrew R Collins Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Markus Weiler; Jonas Blaes; Stefan Pusch; Felix Sahm; Marcus Czabanka; Sebastian Luger; Lukas Bunse; Gergely Solecki; Viktoria Eichwald; Manfred Jugold; Sibylle Hodecker; Matthias Osswald; Christoph Meisner; Thomas Hielscher; Petra Rübmann; Philipp-Niklas Pfenning; Michael Ronellenfitsch; Tore Kempf; Martina Schnölzer; Amir Abdollahi; Florian Lang; Martin Bendszus; Andreas von Deimling; Frank Winkler; Michael Weller; Peter Vajkoczy; Michael Platten; Wolfgang Wick Journal: Proc Natl Acad Sci U S A Date: 2013-12-23 Impact factor: 11.205
Authors: Yukiko Kiniwa; Jiang Li; Mingjun Wang; Chuang Sun; Jeffrey E Lee; Rong-Fu Wang; Helen Y Wang Journal: PLoS One Date: 2015-05-20 Impact factor: 3.240
Authors: Vladimir Lazar; Chen Suo; Cedric Orear; Joost van den Oord; Zsofia Balogh; Justine Guegan; Bastien Job; Guillaume Meurice; Hugues Ripoche; Stefano Calza; Johanna Hasmats; Joakim Lundeberg; Ludovic Lacroix; Philippe Vielh; Fabienne Dufour; Janne Lehtiö; Rudolf Napieralski; Alexander Eggermont; Manfred Schmitt; Jacques Cadranel; Benjamin Besse; Philippe Girard; Fiona Blackhall; Pierre Validire; Jean-Charles Soria; Philippe Dessen; Johan Hansson; Yudi Pawitan Journal: BMC Med Genomics Date: 2013-12-03 Impact factor: 3.063