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.

MATERIALS AND 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: Yasutaka Shuno, Nelson H Tsuno, Yurai Okaji, Takeshi Tsuchiya, Daisuke Sakurai, Takeshi Nishikawa, Naoyuki Yoshikawa, Kazuhito Sasaki, Kumiko Hongo, Giichiro Tsurita, Eiji Sunami, Joji Kitayama, Katsushi Tokunaga, Koki Takahashi, Hirokazu Nagawa
• Journal: The Journal of surgical research (J Surg Res) Vol. 161 Issue 1 Pg. 76-82 (Jun 01 2010) ISSN: 1095-8673 [Electronic] United States
• PMID: 19515385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• Extracellular Matrix Proteins
• ID1 protein, human
• Inhibitor of Differentiation Protein 1
• Inhibitor of Differentiation Proteins
• Integrins
• Neoplasm Proteins
• ID3 protein, human

Topics

• Carcinoma (metabolism, therapy)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Down-Regulation
• Extracellular Matrix Proteins (metabolism)
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Humans
• Inhibitor of Differentiation Protein 1 (genetics, metabolism)
• Inhibitor of Differentiation Proteins (genetics, metabolism)
• Integrins (metabolism)
• Neoplasm Metastasis
• Neoplasm Proteins (genetics, metabolism)
• Pancreatic Neoplasms (metabolism, therapy)
• RNA Interference