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Reexpression of LSAMP inhibits tumor growth in a preclinical osteosarcoma model

ABSTRACT: Osteosarcomas are the most common primary malignant tumors of bone, showing complex chromosomal rearrangements with multiple gains and losses. A frequent deletion within the chromosomal region 3q13.31 has been identified by us and others, and is mainly reported to be present in osteosarcomas. We have previously proposed the gene limbic-system associated membrane protein (LSAMP) as the target for the deletion. In the present study, we found reduced copy number of LSAMP in 45/76 osteosarcoma samples, reduced expression level in 26/42 samples and protein expression in 9/42 samples. The high observed frequency of the deletion and the specificity indicates that it is important for the development of osteosarcomas. By restoring the expression of LSAMP in a cell line with a homozygous deletion of the gene, the proliferation rate in vitro was significantly reduced and tumor growth in vivo was significantly delayed. In response to reexpression of LSAMP, mRNA expression profiling revealed consistent upregulation of the genes hairy and enhancer of split 1 (HES1), cancer/testis antigen 2 (CTAG2) and kruppel-like factor 10 (KLF10). Based on these findings, the tumor suppressor function of LSAMP is most likely exerted by reducing the proliferation rate of the tumor cells, possibly by indirectly upregulating one or more of the genes HES1, CTAG2 or KLF10. To our knowledge, this study describes novel functions of LSAMP, a first step to the understanding of its specific deletion in osteosarcomas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52089 | GEO | 2014/12/31

SECONDARY ACCESSION(S): PRJNA226647

REPOSITORIES: GEO

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