Esophageal Squamous Cell Carcinoma (ESCC) is a common kind of cancer arising from the esophagus. Early studies show that chromosome 14q is commonly involved in ESCC development. In our previous studies, chromosome 14 was transferred into an ESCC cell line, SLMT, by a microcell-mediated chromosome transfer (MMCT) technique. The resultant microcell hybrids (MCHs) displayed delayed tumor growth in in vivo nude mouse tumorigenicity assays. By comparing the differential gene expression profiles of MCHs and tumor segregants, which arose after a long selection period in the mice, one candidate tumor suppressor gene, Latent TGF-β Binding Protein 2 (LTBP-2), was identified. It is up-regulated in MCHs, but is down-regulated in tumors. This evidence suggests LTBP-2 may play a role in tumor suppres...[ Read more ]

Esophageal Squamous Cell Carcinoma (ESCC) is a common kind of cancer arising from the esophagus. Early studies show that chromosome 14q is commonly involved in ESCC development. In our previous studies, chromosome 14 was transferred into an ESCC cell line, SLMT, by a microcell-mediated chromosome transfer (MMCT) technique. The resultant microcell hybrids (MCHs) displayed delayed tumor growth in in vivo nude mouse tumorigenicity assays. By comparing the differential gene expression profiles of MCHs and tumor segregants, which arose after a long selection period in the mice, one candidate tumor suppressor gene, Latent TGF-β Binding Protein 2 (LTBP-2), was identified. It is up-regulated in MCHs, but is down-regulated in tumors. This evidence suggests LTBP-2 may play a role in tumor suppression in ESCC.

LTBP-2 maps to 14q24 and is a secreted protein, which acts as a component of the extracellular matrix. LTBP-2 expression is down-regulated in ESCC cell lines, as compared with an immortalized esophageal epithelial cell line. In ESCC patients’ tumor tissues, LTBP-2 is also down-regulated, when compared to their matched non-tumor tissues. In the in vitro colony formation and three dimensional culture assays, LTBP-2 decreases the colony forming abilities of ESCC cell lines. LTBP-2 is also involved in the reduction of cell migrating and angiogenic abilities of ESCC cell line, and in the migration and tube formation assays. In the in vivo nude mouse assay, LTBP-2 induces tumor suppression. Clonal bisulfite sequencing shows hypermethylation in the LTBP-2 promoter of ESCC cell lines, which suggests that promoter hypermethylation may play a role in inactivation of LTBP-2. Tissue microarray immunohistochemical staining analysis was performed. LTBP-2 expression levels were lower in tumor tissues compared to normal tissues. For patients with differentiated or metastatic tumors, those with higher LTBP-2 expression levels had a shorter survival time. Thus, LTBP-2 appears to have an important role in ESCC development.