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Human Chondrosarcoma Cell Line (human + chondrosarcoma_cell_line)

Distribution by Scientific Domains

Life Sciences	57%
Medical Sciences	28%

Selected Abstracts

Suppression of urokinase receptor expression by bikunin is associated with inhibition of upstream targets of extracellular signal-regulated kinase-dependent cascade

FEBS JOURNAL, Issue 16 2002
Hiroshi Kobayashi
Our laboratory showed that bikunin, a Kunitz-type protease inhibitor, suppresses 4,-phorbol 12-myristate 13-acetate (PMA)- or tumor necrosis factor-alpha (TNF,)-induced urokinase-type plasminogen activator (uPA) expression in different cell types. In addition to its effects on protease inhibition, bikunin could be modulating other cellular events associated with the metastatic cascade. To test this hypothesis, we examined whether bikunin was able to suppress the expression of uPA receptor (uPAR) mRNA and protein in a human chondrosarcoma cell line, HCS-2/8, and two human ovarian cancer cell lines, HOC-I and HRA. The present study showed that (a) bikunin suppresses the expression of constitutive and PMA-induced uPAR mRNA and protein in a variety of cell types; (b) an extracellular signal-regulated kinase (ERK) activation system is necessary for the PMA-induced increase in uPAR expression, as PD098059 and U0126, which prevent the activation of MEK1, reduce the uPAR expression; (c) bikunin markedly suppresses PMA-induced phosphorylation of ERK1/2 at the concentration that prevents uPAR expression, but does not reduce total ERK1/2 antigen level; (d) bikunin has no ability to inhibit overexpression of uPAR in cells treated with sodium vanadate; and (e) we further studied the inhibition of uPAR expression by stable transfection of HRA cells with bikunin gene, demonstrating that bikunin secretion is necessary for inhibition of uPAR expression. We conclude that bikunin downregulates constitutive and PMA-stimulated uPAR mRNA and protein possibly through suppression of upstream targets of the ERK-dependent cascade, independent of whether cells were treated with exogenous bikunin or transfected with bikunin gene. [source]

siRNA mediated inhibition of MMP-1 reduces invasive potential of a human chondrosarcoma cell line

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005
Xiaoling Jiang
Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion and metastasis. Expression of MMP-1 has been reported as a prognostic predictor of recurrence in human chondrosarcoma, and studies using human chondrosarcoma cell lines indicate that MMP-1 expression levels correlate with in vitro invasiveness. These observations suggest that MMP-1 activity has a central role in cell egress from the primary tumor at an early step in the metastatic cascade. In this study, siRNA was used to investigate whether knock down of the MMP-1 gene could be used to inhibit invasiveness in a human chondrosarcoma cell line. The inhibitory effect of siRNA on endogenous MMP-1 gene expression and protein synthesis was demonstrated via RT-PCR, Northern blotting, Western blotting, collagenase activity assay, and an in vitro cell migration assay. The siRNA inhibited MMP-1 expression specifically, since it did not affect the expression of endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) nor other collagenases. Most importantly, the siRNA mediated reduction in MMP-1 expression correlated with a decreased ability of chondrosarcoma cells to invade a Type I collagen matrix. The reduction of invasive behavior demonstrated by human chondrosarcoma cells transfected with MMP-1 siRNA and the specificity of this inhibition supports the hypothesis that this metalloproteinase molecule is involved in initiation of chondrosarcoma metastasis. © 2004 Wiley-Liss, Inc. [source]

Bcl-3 is an interleukin-1,responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene

ARTHRITIS & RHEUMATISM, Issue 12 2002
Sarah F. Elliott
Objective To define the role of Bcl-3, a member of the inhibitor of nuclear factor ,B (NF-,B) family and a known regulator of NF-,B, in interleukin-1 (IL-1),induced matrix metalloproteinase 1 (MMP-1) transcription in chondrocytes and synovial fibroblasts. Methods SW-1353 cells, a human chondrosarcoma cell line, were stimulated with IL-1,, and the harvested RNA was subjected to microarray analysis and quantitative real-time reverse transcription,polymerase chain reaction (RT-PCR). The SW-1353 cells were stimulated with IL-1 or transfected with a plasmid that constitutively expressed Bcl-3, and then MMP-1 messenger RNA (mRNA) expression was assayed by quantitative real-time RT-PCR. SW-1353 cells were transfected with antisense oligonucleotides to Bcl-3, and IL-1,induced MMP-1 mRNA expression was assayed by quantitative RT-PCR. SW-1353 cells and rabbit synovial fibroblasts were transfected with a 4.3-kb human MMP-1 promoter construct along with Bcl-3 and NF-,B1 expression constructs, and MMP-1 transcription was assayed. Results Microarray analysis and real-time RT-PCR showed Bcl-3 to be an IL-1,,responsive gene in SW-1353 cells. Exogenous expression of Bcl-3 in SW-1353 cells activated MMP-1 transcription. Endogenous Bcl-3 expression was required for IL-1, induction of MMP-1 gene expression. Bcl-3 also activated MMP-1 transcription in primary synovial fibroblasts. We showed previously that NF-,B1 contributes to IL-1, induction of MMP-1 transcription in stromal cells. We showed here that Bcl-3 can cooperate with NF-,B1 to activate MMP-1 transcription in SW-1353 cells. Conclusion These data define a new role for Bcl-3 in joint cells as an IL-1,,responsive early gene involved in cell-mediated cartilage remodeling. Our findings implicate Bcl-3 as an important contributor to chronic inflammatory disease states, such as osteoarthritis and rheumatoid arthritis. [source]

siRNA mediated inhibition of MMP-1 reduces invasive potential of a human chondrosarcoma cell line

Targeting of cell survival genes using small interfering RNAs (siRNAs) enhances radiosensitivity of Grade II chondrosarcoma cells

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2007
Dae Won Kim
Abstract The main treatment for chondrosarcoma is surgical resection with a wide margin. However, there are certain chondrosarcomas, such as those found in the pelvis and the spine, which cannot be resected adequately with surgery alone. Unfortunately, most chondrosarcomas are resistant to radiation and chemotherapy. Radiation and chemotherapy are thought to kill chondrosarcoma cells by inducing apoptosis, or programmed cell death. In this article, we hypothesize that antiapoptotic gene silencing enhances radiosensitivity in chondrosarcoma cells by facilitating apoptotic pathways. We knocked down antiapoptotic genes in chondrosarcoma cells using small interfering RNAs (siRNAs). Two well-established Grade II human chondrosarcoma cell lines were pretreated with siRNAs that specifically target mRNAs for Bcl-2, Bcl-xL, or XIAP. The cells were then treated with radiation. Cell death was assessed by flow cytometry. Cell survival and proliferation were measured by clonogenic survival assays. Chondrosarcoma cells exhibited radioresistance and increased the expression of Bcl-2, Bcl-xL, and XIAP in response to radiation. When one of the Bcl-2, Bcl-xL, or XIAP genes was silenced with the corresponding siRNA, radiosensitivity increased up to 9.2-fold (p,<,0.05). When two out of the three antiapoptotic mRNAs were knocked down simultaneously, there was an 11.3-fold increase in cell death after radiation (p,<,0.05). Our findings support a novel therapeutic concept that gene silencing may be used as a molecular adjuvant therapy for radioresistant sarcomas. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25: 820,828, 2007 [source]

Development of chondrosarcoma animal models for assessment of adjuvant therapy

ANZ JOURNAL OF SURGERY, Issue 5 2009
J. C. M. Clark
Abstract Chondrosarcoma is a primary cancer of bone causing significant morbidity due to local recurrence and limited treatment options. Relatively few chondrosarcoma animal models have been developed, and the only orthotopic model is technically demanding and has limited clinical relevance. The aim of this review is to assess the features of current animal chondrosarcoma models for the purpose of developing new models in which to test adjuvant chondrosarcoma therapy. The available literature on this topic was identified using the PubMed database, and then analysed for relevance to the human chondrosarcoma disease and feasibility in testing new therapeutic agents. Animal-derived chondrosarcoma models comprise predominantly allograft tumour transplanted into the rat (Swarm rat chondrosarcoma) or the hamster. These types of models are less relevant to the human disease and have been more useful for evaluation of chondrosarcoma growth and histology than in developing novel therapeutic agents. The athymic nude mouse has enabled reliable human xenograft transplantation. A number of human chondrosarcoma cell lines have been successfully used to generate tumours in this species, including OUMS-27 and HCS-2/A. Although effective in demonstrating anti-tumour effects of a number of agents, the lack of a representative orthotopic model diminishes overall clinical relevance. More clinically relevant models of human chondrosarcoma progression are required either through transgenic mice or orthotopic human xenograft models. [source]