Osteosarcoma is the most common type of primary bone cancer in children and young adults. The prognosis of osteosarcoma is very poor when it is diagnosed with metastasis. Lysosomal‑associated membrane protein 3 (LAMP3) is a tumor‑specific protein induced by hypoxia, which stimulates invasion and metastasis of various cancer cells via hypoxia‑inducible factor (HIF). A previous study from our group has reported that expression of LAMP3 is significantly increased in lung metastatic osteosarcoma compared with primary osteosarcoma using microarray analysis, suggesting that LAMP3 may be involved in metastatic osteosarcoma. The present study therefore aimed to investigate the role of LAMP3 in osteosarcoma metastasis. Knockdown of LAMP3 decreased the invasion of two osteosarcoma cell lines in vitro. Furthermore, knockdown of LAMP3 increased the expression of secreted phosphoprotein 1 (SPP1), cadherin 1, and keratin 19, while it decreased the expression of matrix metallopeptidase 2, collagen type III α 1, twist family bHLH transcription factor 1 and cadherin 2. Concurrent knockdown of SPP1 and LAMP3 attenuated the changes in gene expression profile induced by LAMP3 knockdown alone. Gene ontology and KEGG analysis demonstrated that SPP1 was involved in cell adhesion, focal adhesion, and extracellular matrix‑receptor interaction. In conclusion, the present results suggest that LAMP3 may be involved in the invasion and metastasis of osteosarcoma via regulating signaling downstream of SPP1. Thus, LAMP3/SPP1 signaling may serve as a potential target in the future to prevent osteosarcoma metastasis.

Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young adults under the age of 20. Metastasis is considered an important factor underlying cancer-associated morbidity and mortality, and, as a result, the survival rate of patients with metastatic OS is low. In spite of this, the mechanisms underlying metastasis in OS are currently not well understood. The present study compared gene expression levels between five non-metastatic and four metastatic OS tumor samples, using an Affymetrix microarray. A total of 282 genes were differentially expressed in the metastatic samples, as compared with the non-metastatic samples. Of these differentially expressed genes (DEGs), 212 were upregulated and 70 were downregulated. The following DEGs were associated with metastasis: Homeobox only protein; lysosomal-associated membrane protein-3; chemokine (C-C motif) ligand-18; carcinoembryonic antigen-related cell adhesion molecule-6; keratin-19; prostaglandin-endoperoxide synthase-2; clusterin; and nucleoside diphosphate kinase-1. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were conducted, which identified 529 biological processes (P<0.01) and 10 KEGG pathways (P<0.05) that were significantly over-represented in the metastatic samples, as compared with the non-metastatic samples. Interaction networks for the DEGs were constructed using the corresponding GO terms and KEGG pathways, and these identified numerous genes that may contribute to OS metastasis. Among the enriched biological processes, four DEGs were consistently over-represented: Jun proto-oncogene, caveolin-1, nuclear factor-κB-inhibitor-α and integrin alpha-4; thus suggesting that they may have key roles in OS metastasis, and may be considered potential therapeutic targets in the treatment of patients with OS.