The ECM protein LTBP-2 is a suppressor of esophageal squamous cell carcinoma tumor formation but higher tumor expression associates with poor patient outcome.
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.
Chan
Stephen Ho Kin
SH
Department of Biology, Hong Kong University of Science and Technology, HKSAR, People's Republic of China.
Yee Ko
Josephine Mun
JM
Chan
Kwok Wah
KW
Chan
Yuen Piu
YP
Tao
Qian
Q
Hyytiainen
Marko
M
Keski-Oja
Jorma
J
Law
Simon
S
Srivastava
Gopesh
G
Tang
Johnny
J
Tsao
Sai Wah
SW
Chen
Han
H
Stanbridge
Eric J
EJ
Lung
Maria Li
ML
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014410:Tumor Stem Cell Assay
C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins