Mesenchymal mode of migration participates in pulmonary metastasis of mouse osteosarcoma LM8

Yui, Yoshihiro; Itoh, Kazuyuki; Yoshioka, Kiyoko; Naka, Norifumi; Watanabe, Motonobu; Hiraumi, Yoshimi; Matsubara, Hiroshi; Watanabe, Kenichiro; Sano, Kazumi; Nakahata, Tatsutoshi; Adachi, Souichi

doi:10.1007/s10585-010-9352-x

Cited by 33 publications

(46 citation statements)

References 37 publications

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“…26 These findings strongly suggest that PP2A Cα has an important role in the acquisition of distinct cell morphology in LM8 cells. In addition, LM8 cells display higher levels of FAK phosphorylation at focal adhesion sites, 8 which has key roles in cell migration and metastasis of tumor ) Cells were exposed to serum-free medium for the indicated periods and the collected cell lysates were subjected to western blot analysis using specific antibodies. The cleaved forms of caspase-3 and PARP are pointed by the arrow.…”

Section: Discussionmentioning

confidence: 99%

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Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Yang

Okamura

Morimoto

et al. 2016

Laboratory Investigation

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Osteosarcoma is the most frequent primary bone tumor. Serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction. In this study, we examined the expression and function of PP2A Cα in osteosarcoma cells. PP2A Cα expression was expected to be higher in malignant osteosarcoma tissues. PP2A Cα expression level and PP2A activity was higher in malignant osteosarcoma LM8 cells compared with that in primary osteoblasts and in the osteoblast-like cell line MC3T3-E1. Okadaic acid, an inhibitor of PP2A, reduced cell viability and induced apoptosis in LM8 cells. PP2A Cα-knockdown LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial structures than that in original LM8 cells. Focal adhesion kinase phosphorylation and NF-κB activity decreased in shPP2A-treated cells. Sensitivity to serum deprivation-induced apoptosis increased in shPP2A-treated cells, accompanied by a lower expression level of anti-apoptotic BCL-2 in these cells. Reduction of PP2A Cα resulted in a decrease in the migration ability of LM8 cells in vitro. Reduction in PP2A Cα levels in vivo suppressed proliferation and metastasis in LM8 cells. PP2A Cα expression was also higher in human osteosarcoma MG63 and SaOS-2 cells than that in primary osteoblasts and MC3T3-E1 cells, and reduction in PP2A Cα levels suppressed the cell proliferation rate and migration ability of MG63 cells. These results indicate that PP2A Cα has a critical role in the proliferation and metastasis of osteosarcoma cells; therefore, its inhibition could potentially suppress the malignancy of osteosarcoma cells.

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Section: Discussionmentioning

confidence: 99%

“…6 LM8 cells were also reported to possess activated focal adhesion kinase (FAK) and high NF-κB activity. 7,8 Therefore, LM8 cells could be a useful tool to study the mechanisms involved in proliferation and metastasis of osteosarcoma.…”

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confidence: 99%

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Yang

Okamura

Morimoto

et al. 2016

Laboratory Investigation

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“…Single migration consists of two alternative mechanisms of migration, namely amoeboid and mesenchymal migration (45). According to a report by Yui et al (46), acquisition of the mesenchymal mode of migration is critical in pulmonary metastasis of OS, which is mesenchymal in origin. This report also demonstrated that Rho-associated kinase (ROCK) inhibitor increases OS cell migration with induction of migration mode from amoeboid to mesenchymal (46).…”

Section: Discussionmentioning

confidence: 99%

“…According to a report by Yui et al (46), acquisition of the mesenchymal mode of migration is critical in pulmonary metastasis of OS, which is mesenchymal in origin. This report also demonstrated that Rho-associated kinase (ROCK) inhibitor increases OS cell migration with induction of migration mode from amoeboid to mesenchymal (46). PKD1 is activated by RhoA via ROCK, which has a serine/threonine domain (47), and Matsumoto et al reported that highly activated Rho-ROCK pathway inhibited OS cell invasion and migration with decreasing MMP2 activity (48).…”

Section: Discussionmentioning

confidence: 99%

PKD1 negatively regulates cell invasion, migration and proliferation ability of human osteosarcoma

et al. 2012

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Abstract. Osteosarcoma (OS) is a primary malignancy of the bone, with a tendency to metastasize early. Despite intensive chemotherapy and surgical resection, more than 30% of patients develop distant metastases, and the prognosis of patients with metastases is essentially poor. Members of the protein kinase D (PKD) family are serine/threonine kinases, and have been studied in various cancers. Among the three different isoforms of this family, PKD1 is one of the best understood for its role in human malignancies; however, its role in musculoskeletal tumors has not been studied. In the present study, we investigated the role of PKD1 in human OS. We first analyzed PKD1 mRNA expression in human musculoskeletal tumor tissue samples by quantitative real-time PCR. PKD1 expression in OS samples was significantly lower than that in benign schwannoma samples, and this was correlated with metastatic potential. In in vitro studies, overexpression of PKD1 by plasmid transfection decreased OS cell invasion, migration and proliferation, and significantly decreased matrix metalloproteinase (MMP)2 mRNA expression. Conversely, siRNA knockdown of PKD1 increased invasion, migration and proliferation of OS cells, and MMP2 expression was markedly increased. Furthermore, overexpression of PKD1 significantly reduced in vivo tumor growth of OS cells. These results demonstrated that low expression of PKD1 may contribute to increased cell invasion, migration and proliferation ability of human OS. Taken together, our findings strongly suggest that PKD1 may negatively regulate the malignant potential of human OS, and may be a therapeutic target for human OS in the clinical setting.

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“…Note Yui et al (2010) developed a highly metastatic osteosarcoma cell line through in vivo selection which, in comparison with the parental line, demonstrated higher levels of activated FAK and cdc42. Hanada et al (2005) showed localization of phosphorylated FAK at the infiltrative edge in a three dimensional culture model using invasive murine fibrosarcoma cells.…”

Section: Soft Tissues Bone and Hematolymphoid Tissuesmentioning

confidence: 99%

PTK2 (PTK2 protein tyrosine kinase 2)

Schwock¹,

Dhani²

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Mesenchymal mode of migration participates in pulmonary metastasis of mouse osteosarcoma LM8

Cited by 33 publications

References 37 publications

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

PKD1 negatively regulates cell invasion, migration and proliferation ability of human osteosarcoma

PTK2 (PTK2 protein tyrosine kinase 2)

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