Characterization of LSAMP, a novel candidate tumor suppressor gene in osteosarcomas

Abstract

Osteosarcomas are the most common primary malignant tumors of bone. They are highly aggressive with poor prognosis, and display complex genomic aberrations. Previously, our group has identified a frequently deleted region in 3q13.31 in osteosarcoma tumors and cell lines. The region contains the gene encoding the limbic-system associated membrane protein (LSAMP), which previously has been reported to be a candidate tumor suppressor gene in other cancer types, and subsequently also in osteosarcomas.

In this study, aberrations of LSAMP have been further investigated in osteosarcoma clinical samples, xenografts and cell lines. Heterozygous deletion of LSAMP was observed in 32 % (5/16) of the samples investigated. Furthermore, 39 % (11/28) had reduced expression level of LSAMP and the LSAMP protein was detected by western blotting in 33 % (10/30) of the osteosarcoma samples investigated.

To examine the possible function of LSAMP, the expression of this gene was restored in an osteosarcoma cell line with a homozygous deletion and following lack of expression. The results indicate that over-expression of LSAMP decreases the proliferation rate, which is consistent with what others have reported. The migration rate and colony forming capability of the cells were unaffected. Interestingly, by gene expression profiling, the genes CTAG2, HES1 and KLF10 were commonly up-regulated in response to LSAMP expression in the seven, randomly chosen clones investigated.

The results indicate that the LSAMP protein might up-regulate the transcription of HES1 and KLF10, and that LSAMP alone, or in conjunction with other genes, suppresses tumors by reducing their proliferation rate. Together, our data strengthens the hypothesis of LSAMP being a tumor suppressor gene in osteosarcomas.