Novel cell lines established from a human myxoid malignant fibrous histiocytoma arising in the uterus

Kiyozuka, Yasuhiko; Nakagawa, Hiroyuki; Uemura, Yoshiko; Senzaki, Hideto; Yamamoto, Akira; Noguchi, Taketoshi; Mizuta, H.; Nakanishi, Kohji; Nakano, Shiro; Tsubura, Airo

doi:10.1016/s0165-4608(00)00413-1

Cited by 21 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KTHOS and TNMY-1 were previously established at our laboratory 49,50 . The Nara-H cell line was obtained from ScienStuff Co. (Nara, Japan) 51 . MG-63 was purchased from the American Type Culture Collection.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Mitochondrial Proliferation by PGC-1α Induces Cellular Apoptosis in Musculoskeletal Malignancies

Onishi

Ueha

Kawamoto

et al. 2014

Sci Rep

View full text Add to dashboard Cite

A number of studies have reported that decreased mitochondrial numbers are linked with neoplastic transformation and/or tumor progression, including resistance to apoptosis. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a multi-functional transcriptional coactivator that regulates the activities of multiple nuclear receptors and transcriptional factors involved in mitochondrial biogenesis. In this study, we observed that the number of mitochondria in sarcoma tissues, such as osteosarcoma and malignant fibrous histiocytoma, is significantly lower than that in normal muscle tissue or benign tumors, and that increasing the number of mitochondria by PGC-1a overexpression induces mitochondrial apoptosis in human sarcoma cell lines. The findings suggest that decreased mitochondrial numbers may contribute to musculoskeletal tumor progression, and that regulation of mitochondrial numbers by PGC-1a could be a potent therapeutic tool for human malignancies.M usculoskeletal malignancies are clinically aggressive and have high metastatic behavior in various organs. Although many chemotherapeutic protocols are used for human sarcomas, the current chemotherapeutic strategies for high-grade sarcomas have been ineffective, and the prognoses of patients can be extremely poor because of local recurrence and distant metastases 1 . Therefore, new therapeutic strategies against high-grade sarcomas need to be established. We have previously reported several therapeutic strategies against high-grade sarcomas [2][3][4] . Mitochondria are cytoplasmic organelles that play essential roles in cellular energy metabolism and programmed cell death 5 . Although the majority of mitochondrial proteins are synthesized by nuclear DNA (nDNA), mitochondria possess their own genome, called mitochondrial DNA (mtDNA) 6 . Thousands of mitochondria are found in each cell, and the number of mitochondria per cell is known to vary with cell or tissue origin, and to change under different internal or external microenvironments, such as hypoxia, and stimulation by steroid hormones 7,8 . Quantitative changes in mitochondrial numbers have been observed in many cancers as a decrease in hepatocellular carcinoma, renal cell carcinoma, advanced gastric cancer and breast cancer [9][10][11][12][13][14] , or an increase in head and neck cancers, ovarian cancer, and esophageal squamous cell carcinoma [15][16][17]

show abstract

Section: Methodsmentioning

confidence: 99%

Regulation of Mitochondrial Proliferation by PGC-1α Induces Cellular Apoptosis in Musculoskeletal Malignancies

Onishi

Ueha

Kawamoto

et al. 2014

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The Nara-H cell line was established from a myxoid MFH of the uterus by Kiyozuka et al (21). The cells were grown in Dulbecco’s modified Eagle’s medium (DMEM; Sigma-Aldrich, St. Louis, MO, USA) containing 10% fetal bovine serum (FBS; Sigma-Aldrich) and 100 U/ml penicillin.…”

Section: Methodsmentioning

confidence: 99%

The combination of rapamycin and MAPK inhibitors enhances the growth inhibitory effect on Nara-H cells

Nakamura

Hitora

Yamagami

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway promotes the initiation of autophagy, and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase (ERK) is well known to induce autophagy. Autophagy is a self-defense mechanism of cancer cells that are subjected to antitumor agents, and blocking autophagy can trigger apoptosis. In the present study, we demonstrate that an mTOR inhibitor, rapamycin, induces autophagy in the Nara-H malignant fibrous histiocytoma (MFH) cell line through the activation of ERK1/2. Rapamycin-induced apoptosis was enhanced following the inhibition of the MEK/ERK pathway. In the Nara-H cells, we examined the effects of rapamycin treatment on cell proliferation and on the phosphorylation of the mTOR pathway components and autophagy by western blot analysis. Furthermore, we examined the effects of rapamycin with or without the MEK inhibitor, U0126, on the induction of apoptosis by using fluorescence microscopy. Rapamycin inhibited Nara-H cell proliferation and decreased the phosphorylation of the mTOR pathway in the Nara-H cells. Rapamycin induced the apoptosis of Nara-H cells, and this apoptosis was enhanced by U0126. Simultaneously, phospho-ERK1/2 was activated by rapamycin. The present study demonstrates that rapamycin induces autophagy in Nara-H cells by activating the MEK/ERK signaling pathway, and the rapamycin-induced apoptosis can be enhanced by the MEK inhibitor, U0126. These results suggest that self-protective mechanisms involving mTOR inhibitors in Nara-H cells are prevented by the inhibition of the MEK/ERK pathway. The combination of an mTOR inhibitor (e.g., rapamycin) and an MEK inhibitor (e.g., U0126) may offer effective treatment for MFH, as this combination effectively activates apoptotic pathways.

show abstract

“…Two human MFH cell lines (Nara-H and TNMY1) were used for in vitro studies. Nara-H were purchased from ScienStuff Co., Nara, Japan (15), and TNMY1 cells were previously established in our laboratory (16). Cells were grown in culture medium consisting of DMEM (Sigma-Aldrich Co., St. Louis, MO, USA) supplemented with 10% fetal bovine serum (Sigma-Aldrich) and 100 U/ml penicillin/streptomycin solution (Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma

Fukase

Kawamoto

Kishimoto³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. Protein kinase Cδ (PKCδ), an isoform of PKC, has been shown to act as a critical mediator of tumor progression and apoptosis; however, its role in musculoskeletal tumors is still unknown. In the current study, we examined the expression of PKCδ in human musculoskeletal tumor tissue samples, and investigated the effects of siRNA downregulation of PKCδ on human malignant fibrous histiocytoma (MFH) cell proliferation, migration, and apoptosis, to elucidate its functional roles in musculoskeletal tumorigenesis. Of note, real-time PCR analysis revealed that mRNA expression of PKCδ in highgrade musculoskeletal MFH tumors was significantly lower than that in benign schwannomas. siRNA downregulation of PKCδ significantly increased human MFH cell proliferation and migration, and markedly suppressed apoptosis. These findings suggest that PKCδ has a negative effect on tumori genesis and/ or acts as a pro-apoptotic kinase in human MFH cells. The data presented here could be applied in the development of new therapeutic avenues, with the elevation of PKCδ expression being one potential strategy to prevent MFH progression. Thus, PKCδ may be a potent therapeutic target for human MFH.

show abstract

Novel cell lines established from a human myxoid malignant fibrous histiocytoma arising in the uterus

Cited by 21 publications

References 38 publications

Regulation of Mitochondrial Proliferation by PGC-1α Induces Cellular Apoptosis in Musculoskeletal Malignancies

Regulation of Mitochondrial Proliferation by PGC-1α Induces Cellular Apoptosis in Musculoskeletal Malignancies

The combination of rapamycin and MAPK inhibitors enhances the growth inhibitory effect on Nara-H cells

Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma

Contact Info

Product

Resources

About