title: Id1/Id3 knockdown inhibits metastatic potential of pancreatic cancer.
abstract: BACKGROUND
  The Id (inhibitor of DNA binding/differentiation) proteins belong to the helix-loop-helix transcriptional regulatory factors, and play important roles in tumor development. Previously, we and others have shown that targeting Id in tumor cells could have important clinical implications. In the present study, we aimed to evaluate the effects of Id inhibition in human pancreatic cancer cells.
  
  
  METHODS
  Id1 and Id3 were stably double-knockdown in human pancreatic cancer cell line MIA-Paca2 by means of RNA interference. Expression of Id and integrins were analyzed by flow-cytometry. Cell proliferation was evaluated by MTS assay. Migration was measured by wound closure assay. Adhesion assay was performed to evaluate binding capacity for different extracellular matrix proteins. Finally, in vivo properties of tumor cells were observed in a mouse model of peritoneal metastasis.
  
  
  RESULTS
  Id1/Id3 double-knockdown resulted in decreased ability of pancreatic cancer cells to proliferate and migrate. In addition, Id1/Id3 double-knockdown caused decreased expression of integrins alpha3, alpha6, and beta1, and consequently reduced adhesion of tumor cells to laminin. Finally, peritoneal metastases of Id1/Id3 double-knockdown tumor cells were significantly reduced.
  
  
  CONCLUSIONS
  We concluded that the Id proteins play a pivotal role in the development of peritoneal metastasis of pancreatic cancer, and consequently, their targeting would be a novel strategy for the prevention and treatment of pancreatic cancer.
authors.affiliation: Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. shuu@tkg.att.ne.jp
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Shuno
authors.forename: Nelson H
authors.initials: NH
authors.lastname: Tsuno
authors.forename: Yurai
authors.initials: Y
authors.lastname: Okaji
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sakurai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yoshikawa
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Sasaki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hongo
authors.forename: Giichiro
authors.initials: G
authors.lastname: Tsurita
authors.forename: Eiji
authors.initials: E
authors.lastname: Sunami
authors.forename: Joji
authors.initials: J
authors.lastname: Kitayama
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Koki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000628:therapy; D034622:RNA Interference
chemical_list: D016326:Extracellular Matrix Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D016023:Integrins; D009363:Neoplasm Proteins; C075640:ID3 protein, human