Secreted 70kDa lumican stimulates growth and inhibits invasion of human pancreatic cancer

Tetsushi Yamamoto; Yoko Matsuda; Kiyoko Kawahara; Toshiyuki Ishiwata; Zenya Naito

doi:10.1016/j.canlet.2012.01.023

Secreted 70kDa lumican stimulates growth and inhibits invasion of human pancreatic cancer

Cancer Lett. 2012 Jul 1;320(1):31-9. doi: 10.1016/j.canlet.2012.01.023. Epub 2012 Jan 20.

Authors

Tetsushi Yamamoto¹, Yoko Matsuda, Kiyoko Kawahara, Toshiyuki Ishiwata, Zenya Naito

Affiliation

¹ Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.

PMID: 22266188
DOI: 10.1016/j.canlet.2012.01.023

Abstract

Lumican expression in the stromal tissues of pancreatic ductal adenocarcinoma (PDAC) correlates with tumor invasion, and tends to correlate with poor prognosis. We used gene transfection techniques to examine the biological roles of lumican secreted from PDAC cells. Lumican-transfected PANC-1 cells secreted a 70-kDa lumican protein and had an active ERK pathway. Transfection stimulated PANC-1 cell growth, increased cell adhesion to laminin, inhibited cell invasion, and decreased active matrix metalloproteinase-9. Down-regulation of lumican using siRNA resulted in opposite cell behavior. Thus, the 70-kDa lumican secreted by PDAC cells plays important roles in cell growth and invasion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Pancreatic Ductal / genetics
Carcinoma, Pancreatic Ductal / metabolism*
Carcinoma, Pancreatic Ductal / pathology
Cell Growth Processes / physiology
Cell Line, Tumor
Cell Movement / physiology
Chondroitin Sulfate Proteoglycans / biosynthesis
Chondroitin Sulfate Proteoglycans / genetics
Chondroitin Sulfate Proteoglycans / metabolism*
Down-Regulation
Extracellular Signal-Regulated MAP Kinases / metabolism
Glycosylation
Humans
Integrin alpha3 / biosynthesis
Keratan Sulfate / biosynthesis
Keratan Sulfate / genetics
Keratan Sulfate / metabolism*
Lumican
MAP Kinase Signaling System
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Neoplasm Invasiveness
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / metabolism*
Pancreatic Neoplasms / pathology
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
Transfection

Substances

Chondroitin Sulfate Proteoglycans
Integrin alpha3
LUM protein, human
Lumican
RNA, Small Interfering
Keratan Sulfate
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9