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PMID: 21854747 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Twist1 is up-regulated in gastric cancer-associated fibroblasts with poor clinical outcomes.

The American journal of pathology ·Vol. 179 ·No. 4 ·2011-10-00 ·Pages 1827-38

Sung CO, Lee KW, Han S, Kim SH

Abstract

Stromal fibroblasts perform important roles in cancer development and progression. Overexpression of Twist1, a basic helix-loop-helix transcription factor, is often associated with aggressive behavior in many tumors. In this study, we investigated Twist1 expression patterns in gastric stromal fibroblasts and cancer cells using a monoclonal Twist1 antibody after validating the effectiveness of four commercial Twist1-specific antibodies. Twist1 expression was more frequently observed in gastric cancer-associated fibroblasts (CAFs) than in other cancer cells but was otherwise rarely expressed in noncancerous tissue. In laser capture microdissection of stromal fibroblasts, Twist1 immunopositive fibroblasts exhibited significantly increased Twist1, fibroblast-specific protein 1, and CXCL14 mRNA expression. Furthermore, Twist1 mRNA expression showed a significant linear correlation with that of platelet-derived growth factor receptors β and α. We found that conditioned media from Twist1-expressing skin and lung fibroblasts significantly promote invasion of gastric cancer cells in vitro. In 195 gastric cancer samples, CAF Twist1 expression was associated with tumor size, invasion depth, and lymph node metastasis. Twist1 was also associated with poor prognosis in patients with gastric cancer, particularly in those with the diffuse type. In conclusion, CAFs in gastric cancer frequently have altered Twist1 expression, and increased Twist1 expression in fibroblasts contributes to the progression of cancer cells and poor patient survival.

MeSH Terms
Aged Antibodies, Neoplasm/immunology Cell Line, Tumor Cell Movement DNA Methylation/genetics Female Fibroblasts/metabolism,pathology Gene Expression Regulation, Neoplastic Humans Male Middle Aged Neoplasm Invasiveness Nuclear Proteins/genetics,metabolism Prognosis Promoter Regions, Genetic/genetics Reproducibility of Results Stomach Neoplasms/genetics,immunology,pathology Stromal Cells/metabolism,pathology Survival Analysis Treatment Outcome Twist-Related Protein 1/genetics,metabolism Up-Regulation
Chemicals
Antibodies, Neoplasm Nuclear Proteins TWIST1 protein, human Twist-Related Protein 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sung Chang Ohk
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee Keun-Woo
Han Songying
Kim Seok-Hyung
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
1525-2191
DOI
10.1016/j.ajpath.2011.06.032
Published
2011-10-00
Epub
2011-00-18
Pages
1827-38
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC3181370
Subset
IM
External Links
PubMed source DOI: 10.1016/j.ajpath.2011.06.032 PMC Full Text View journal details
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