Osteosarcoma is the most prevalent histological form of primary malignant bone
tumor. The majority of
osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto-oncogene
serine/threonine-protein kinase PIM1 is associated with growth and survival of many kinds of
tumor cells. However, the role of PIM1 in
osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in
osteosarcoma. We found PIM1 was highly expressed in various
osteosarcoma cell lines and in
tumor tissues from
osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease-free survival rate of patients with high levels of PIM1
protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present
metastasis and can be considered as an independent prognostic factor in
osteosarcoma patients. Knockdown of PIM1 expression by synthetic
siRNA or
shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down-regulation of
anti-apoptotic protein Bcl-2. The similar results were obtained in
osteosarcoma cells treated with PIM1 specific inhibitor (SMI-4a). These results suggest that PIM1
kinase is critical for the growth and
metastasis of
osteosarcoma cells and can be a potential therapeutic target for
osteosarcoma treatment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185-1194, 2016.