Heterogeneous pattern of gene expression in cloned cell lines established from a rat transplantable osteosarcoma lung metastatic nodule

Honoki, Kanya; Mori, Toshio; Tsutsumi, Masahiro; Tsujiuchi, Toshifumi; Kido, Akira; Morishita, Tsuyoshi; Miyauchi, Yoshimasa; Dohi, Yoshiko; Mii, Yoshio; Tamai, Susumu; Konishi, Yoichi

doi:10.1016/s0304-3835(98)00048-2

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…The COS1NR cell line was established from 4-(hydroxyamino)-quinoline 1-oxide-induced transplantable OS in male Fischer 344 (F344) rats (17,18). The cells were cultured in Eagle's Modified Essential Medium (MEM) supplemented with 10% FBS (JRH Biosciences, Lot no.…”

Section: Methodsmentioning

confidence: 99%

Effect of mesenchymal stem cells on hypoxia-induced desensitization of β2-adrenergic receptors in rat osteosarcoma cells

et al. 2012

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Abstract. The β2-adrenergic receptor (β2AR) mediates the effects of chronic stress in several neoplasms, however, β2AR signaling is impaired by hypoxia in various tissues. While hypoxia is a common feature significant in the progression of solid tumors, little is known about the effect of hypoxia on β2AR signaling in the tumor microenvironment. Previously, it has been reported that the systemic administration of mesenchymal stem cells (MSCs) increased the engraftment and metastatic colonization of rat osteosarcoma (OS) cells. In the current study, the effect of MSCs on the hypoxia-induced desensitization of the β2AR in OS cells was investigated. Epinephrine, norepinephrine and isoproterenol increased the cellular proliferation of the rat OS cell line COS1NR and rat MSCs in a dose-dependent and β2AR antagonist-sensitive manner. While isoproterenol had significant proliferative effects on MSCs under normoxic and hypoxic conditions, COS1NR cells did not respond under hypoxic conditions. A sensitivity assay for the β2AR revealed that hypoxia impaired the sensitivity of COS1NR cells, whereas hypoxia did not affect MSCs. An immunoassay revealed no significant change in the expression of hypoxia-inducible factor-1α (HIF1α) in COS1NR cells, whilst an immunoassay demonstrated a 15% increase in MSCs following isoproterenol stimulation. In COS1NR cells co-cultured with MSCs under hypoxic conditions, isoproterenol caused a significant increase in proliferation and this effect was inhibited by an anti-interleukin (IL)-6 antibody. A tumor formation assay in syngeneic rats revealed that the systemic administration of MSCs enhances the growth of OS and the effect of MSCs was inhibited by IL-6 neutralization.In conclusion, MSCs are resistant to the hypoxia-induced desensitization to β2AR. Hypoxia caused a siginificant desensitization of the β2AR in COS1NR cells alone, whereas MSCs may support tumor progression through cellular interactions.

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Section: Methodsmentioning

confidence: 99%

Effect of mesenchymal stem cells on hypoxia-induced desensitization of β2-adrenergic receptors in rat osteosarcoma cells

et al. 2012

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“…Rat osteosarcoma cell line COS1NR was established from chemically-induced osteosarcoma in Fischer 344 rats by 4-hydroxy quinolone 1-oxide in our laboratory (27,28). Rat mesenchymal stem cells (MSCs) were isolated from rat femur bone marrow through the monolayer culture on a plastic dish (29).…”

Section: Methodsmentioning

confidence: 99%

Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model

Tsukamoto

Honoki

Fujii³

et al. 2011

Int J Oncol

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Abstract.Although mesenchymal stem cells (MSCs) are considered to be the cells of origin for most sarcomas, the role of MSCs as a source of tumor stroma is not fully understood in this tumor type. The current study investigated whether MSCs affect the tumor growth and metastatic ability in rat osteosarcoma model. Results from subcutaneous co-implantation of rat osteosarcoma COS1NR cells, established in our laboratory, with rat MSCs isolated from femur bone marrow showed that the incidence of tumor formation and tumor growth rate was higher until 5 weeks compared to COS1NR cell inoculation alone. However, no difference was observed in tumor growth afterwards and in the number of metastatic nodules at 9 weeks (0.75 vs. 1.2). Intravenous MSC injection at weeks 3 and 5 after subcutaneous inoculation of COS1NR cells significantly increased the number of lung nodules in the group with MSC injection compared to the group without MSC injection (17.33 vs. 2.0), while no difference was observed in subcutaneous tumor growth between those groups. Pathway analysis from gene expression profile identified that genes involved in focal adhesion, cytokine-cytokine receptor and extracellular matrix-receptor pathways such as CAMs (ICAM and VCAM)-integrins were highly expressed in MSCs, possibly participating in the tumor progression of osteosarcoma. These results suggest that MSCs could provide a source of microenvironments for osteosarcoma cells, and might enhance the ability of settlement and colonization which lead to early onset of growth and metastasis, possibly through their activated pathways interaction. IntroductionHistoric landmark of tumor microenvironment research was proposed as the 'seed and soil' hypothesis by Stephen Paget 120 years ago (1), and the importance of the microenvironment and stroma in the evolution and progression of solid tumors has drawn renewed interest in recent years. A complex structure of mixed cell types and tissues with endothelial cells, immune cells, stromal cells and extracellular matrix is essential for the growth and progression of solid tumors (2). Although all of these components in the tumor are integral in carcinogenesis and metastasis, the stroma is considered to be a 'co-conspirator' in the evolution and progression of the disease (3). Among the stromal elements, the progenitor cells of the stroma, the mesenchymal stem cells (MSCs), have been receiving focused attention lately.Mesenchymal stem cells (MSCs) are mainly derived from bone marrow, non-hematopoietic precursor cells possessing differentiation potential to skeletal mesodermal lineages such as osteoblasts, chondrocytes and adipocytes as well as some extra-mesodermal cell types including neural, pancreatic and hepatocytic phenotypes with strong proliferative capacity (4-6), and are of increasing interest as the future therapeutic tool in regenerative medicine (7,8). MSCs also display immune suppressive properties which could be the potentially exploited for therapeutic treatment of auto-immune diseases and the reduction of gra...

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“…Rockville, Md, USA). The rat osteosarcoma cell line COS1NR was established from a chemically induced osteosarcoma in a Fischer 344 rat by 4-hydroxy quinolone 1-oxide in our laboratory (10,11). MG63 and COS1NR cells were maintained in dulbecco's minimum essential medium (Nacalai Tesque, Kyoto, Japan) with 10% fetal bovine serum (Nichirei, Tokyo, Japan) and 50 U/ml penicillin/streptomycin (Nacalai Tesque) under 5% CO 2 at 37˚C.…”

Section: Introductionmentioning

confidence: 99%

Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress

et al. 2015

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Abstract. Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with mali gnant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.

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Heterogeneous pattern of gene expression in cloned cell lines established from a rat transplantable osteosarcoma lung metastatic nodule

Cited by 13 publications

References 29 publications

Effect of mesenchymal stem cells on hypoxia-induced desensitization of β2-adrenergic receptors in rat osteosarcoma cells

Effect of mesenchymal stem cells on hypoxia-induced desensitization of β2-adrenergic receptors in rat osteosarcoma cells

Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model

Ubiquilin 2 enhances osteosarcoma progression through resistance to hypoxic stress

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