The ECM protein LTBP-2 is a suppressor of esophageal squamous cell carcinoma tumor formation but higher tumor expression associates with poor patient outcome

Stephen Ho Kin Chan, Josephine Mun Yee Ko, Kwok Wah Chan, Yuen Piu Chan, Qian Tao, Marko Hyytiainen, Jorma Keski-Oja, Simon Law, Gopesh Srivastava, Cheuk On Tang, Sai Wah Tsao, Han Chen, Eric J. Stanbridge, Maria Li Lung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

39 Citations (Scopus)

Abstract

Our previous studies of chromosome 14 transfer into tumorigenic esophageal squamous cell carcinoma (ESCC) cell line, SLMT, suggested the existence of tumor suppressor genes on chromosome 14. Gene expression profiling of microcell hybrids and the tumor segregants identified an interesting gene, LTBP-2 (latent transforming growth factor β binding protein 2), which has been analyzed here for its role in ESCC. LTBP-2 maps to 14q24 and encodes a secreted protein, which is a component of the extracellular matrix microfibrils. LTBP-2 expression was downregulated in ESCC cell lines and tumor tissues. Promoter hypermethylation was found to be involved in LTBP-2 inactivation. Functional studies indicated its tumor-suppressive roles in ESCC. In the in vitro colony formation and Matrigel three-dimensional culture assays, LTBP-2 decreased the colony-forming abilities of ESCC cell lines. LTBP-2 expression was associated with reduction of cell migrating and invasive abilities. LTBP-2 could also reduce the tube-forming ability of endothelial cells. Moreover, LTBP-2 induced tumor suppression in in vivo nude mouse assays. Tissue microarray immunohistochemical staining analysis indicated that LTBP-2 expression is reduced in tumor tissues when compared to normal tissues, and LTBP-2 expression correlated significantly with the survival of ESCC patients. Thus, LTBP-2 appears to play an important role in ESCC.
Original languageEnglish
Pages (from-to)565-573
Number of pages9
JournalInternational Journal of Cancer
Volume129
Issue number3
DOIs
Publication statusPublished - 1 Aug 2011

Keywords

  • antiangiogenesis
  • ESCC
  • extracellular matrix protein
  • hypermethylation
  • invasion
  • LOH
  • LTBP-2
  • microcell-mediated chromosome transfer
  • migration
  • tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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