LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma

Han Chen; Josephine Mun Yee Ko; Victor Chun Lam Wong; Marko Hyytiainen; Jorma Keski-Oja; Daniel Chua; John M Nicholls; Florence Man Fung Cheung; Anne Wing Mui Lee; Dora Lai-Wan Kwong; Pui Man Chiu; Eugene R Zabarovsky; Sai Wah Tsao; Qian Tao; Rebecca Kan; Stephen Ho Kin Chan; Eric J Stanbridge; Maria Li Lung

doi:10.1016/j.canlet.2012.06.005

LTBP-2 confers pleiotropic suppression and promotes dormancy in a growth factor permissive microenvironment in nasopharyngeal carcinoma

Cancer Lett. 2012 Dec 1;325(1):89-98. doi: 10.1016/j.canlet.2012.06.005. Epub 2012 Jun 26.

Authors

Han Chen¹, Josephine Mun Yee Ko, Victor Chun Lam Wong, Marko Hyytiainen, Jorma Keski-Oja, Daniel Chua, John M Nicholls, Florence Man Fung Cheung, Anne Wing Mui Lee, Dora Lai-Wan Kwong, Pui Man Chiu, Eugene R Zabarovsky, Sai Wah Tsao, Qian Tao, Rebecca Kan, Stephen Ho Kin Chan, Eric J Stanbridge, Maria Li Lung

Affiliation

¹ Division of Life Science, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region.

PMID: 22743615
DOI: 10.1016/j.canlet.2012.06.005

Abstract

This study identified LTBP-2 as a pleiotropic tumor suppressor in nasopharyngeal carcinoma, which safeguards against critical malignant behaviors of tumor cells. LTBP-2 expression was significantly decreased or lost in up to 100% of NPC cell lines (7/7) and 80% of biopsies (24/30). Promoter hypermethylation was found to be involved in LTBP-2 silencing. Using a tetracycline-regulated inducible expression system, we unveiled functional roles of LTBP-2 in suppressing colony formation, anchorage-independent growth, cell migration, angiogenesis, VEGF secretion, and tumorigenicity. Three-dimensional culture studies suggested the involvement of LTBP-2 in maintenance of tumor cell dormancy in a growth factor favorable microenvironment.

Publication types

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

MeSH terms

Azacitidine / analogs & derivatives
Azacitidine / pharmacology
Carcinoma
Cell Line, Tumor
Cell Movement / physiology
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
DNA Methylation
Decitabine
Down-Regulation / genetics
Gene Expression Regulation, Neoplastic
Humans
Hydroxamic Acids / pharmacology
Latent TGF-beta Binding Proteins / genetics*
Latent TGF-beta Binding Proteins / metabolism*
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / blood supply
Nasopharyngeal Neoplasms / genetics
Nasopharyngeal Neoplasms / metabolism*
Nasopharyngeal Neoplasms / pathology
Neovascularization, Pathologic / genetics
Neovascularization, Pathologic / metabolism
Promoter Regions, Genetic
Tumor Microenvironment
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism*
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism

Substances

Hydroxamic Acids
LTBP2 protein, human
Latent TGF-beta Binding Proteins
Tumor Suppressor Proteins
VEGFA protein, human
Vascular Endothelial Growth Factor A
trichostatin A
Decitabine
Azacitidine