Knockdown of liver-intestine cadherin decreases BGC823 cell invasiveness and metastasis in vivo.
OBJECTIVE
To assess BGC823 gastric cancer (GC) cell metastasis after knockdown of liver-intestine cadherin (CDH17) and the therapeutic value of CDH17-RNAi-lentivirus in vivo.


METHODS
We evaluated primary tumor growth and assessed local infiltration and systemic tumor dissemination using an orthotopic implantation technique. The therapeutic value of CDH17 knockdown was examined by intratumoral administration of CDH17-RNA interference (RNAi)-lentivirus in an established GC tumor xenograft mouse model. Furthermore, a comparative proteomic approach was utilized to identify differentially expressed proteins in BGC823 and lenti-CDH17-miR-neg cells following CDH17 knockdown.


RESULTS
Metastases in the liver and lung appeared earlier and more frequently in animals with tumors derived from BGC823 or lenti-CDH17-miR-neg cells than in tumors derived from lenti-CDH17-miR-B cells. Average tumor weight and volume in the CDH17-RNAi-lentivirus-treated group were significantly lower than those in the control group (tumor volume: 0.89 ± 0.04 cm³ vs 1.16 ± 0.06 cm³, P < 0.05; tumor weight: 1.15 ± 0.58 g vs 2.09 ± 0.08 g, P < 0.05). Fifteen differentially expressed proteins were identified after CDH17 silencing in BGC823 cells, including a variety of cytoskeletal and chaperone proteins as well as proteins involved in metabolism, immunity/defense, cell proliferation and differentiation, cell cycle, and signal transduction.


CONCLUSIONS
Our data establish a foundation for future studies of the comprehensive protein expression patterns and effects of CDH17 in GC.
Department of Otolaryngology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Yu
Y
Xu
Jin
J
Zhang
Qi-Sheng
QS
Liu
Wei-Guo
WG
Dong
D000818:Animals; D015820:Cadherins / Q000172:deficiency* / Q000235:genetics; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D040901:Proteomics / Q000379:methods; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
C490584:CDH17 protein, human; D015820:Cadherins