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Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines

  • Authors:
    • M. Waheed Roomi
    • Tatiana Kalinovsky
    • Aleksandra Niedzwiecki
    • Matthias Rath
  • View Affiliations / Copyright

    Affiliations: Dr Rath Research Institute, Santa Clara, CA 95050, USA
    Copyright: © Roomi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 39-49
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    Published online on: May 9, 2013
       https://doi.org/10.3892/ijo.2013.1934
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Abstract

Adult sarcomas are highly aggressive tumors that are characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the ECM and basement membrane, allowing cancer cells to spread to distal organs. Proteases play a key role in tumor cell invasion and metastasis by digesting the basement membrane and ECM components. Strong clinical and experimental evidence demonstrates association of elevated levels of u-PA and MMPs with cancer progression, metastasis and shortened patient survival. MMP activities are regulated by specific tissue inhibitors of metalloproteinases (TIMPs). Our main objective was to study the effect of a nutrient mixture (NM) on the activity of u-PA, MMPs and TIMPs in various human adult sarcomas. Human fibrosarcoma (HT-1080), chondrosarcoma (SW-1353), liposarcoma (SW-872), synovial sarcoma (SW-982) and uterine leimyosarcoma (SK-UT-1) cell lines (ATCC) were cultured in their respective media and treated at confluence with NM at 0, 50, 100, 250, 500 and 1,000 µg/ml. Analysis of u-PA activity was carried out by fibrin zymography, MMPs by gelatinase zymography and TIMPs by reverse zymography. Fibrosarcoma, chondrosarcoma, liposarcoma and leiomyosarcoma cancer cell lines expressed u-PA, which was inhibited by NM in a dose‑dependent manner. However, no bands corresponding to u-PA were detected for synovial sarcoma cells. On gelatinase zymography, fibrosarcoma, chondrosarcoma, liposarcoma and synovial sarcoma showed bands corresponding to MMP-2 and MMP-9 with enhancement of MMP-9 with PMA (100 ng/ml) treatment. Uterine leiomyosarcoma showed strong bands corresponding to inactive and active MMP-9 and a faint band corresponding to MMP-9 dimer induced with PMA treatment, but no MMP-2 band. NM inhibited their expression in a dose‑dependent manner. Activity of TIMPs was upregulated by NM in all cancer cell lines in a dose-dependent manner. Analysis revealed a positive correlation between u-PA and MMPs and a negative correlation between u-PA/MMPs and TIMPs. These findings suggest the therapeutic potential of NM in treatment of adult sarcomas.
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Copy and paste a formatted citation
Spandidos Publications style
Roomi MW, Kalinovsky T, Niedzwiecki A and Rath M: Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines. Int J Oncol 43: 39-49, 2013.
APA
Roomi, M.W., Kalinovsky, T., Niedzwiecki, A., & Rath, M. (2013). Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines. International Journal of Oncology, 43, 39-49. https://doi.org/10.3892/ijo.2013.1934
MLA
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines". International Journal of Oncology 43.1 (2013): 39-49.
Chicago
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines". International Journal of Oncology 43, no. 1 (2013): 39-49. https://doi.org/10.3892/ijo.2013.1934
Copy and paste a formatted citation
x
Spandidos Publications style
Roomi MW, Kalinovsky T, Niedzwiecki A and Rath M: Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines. Int J Oncol 43: 39-49, 2013.
APA
Roomi, M.W., Kalinovsky, T., Niedzwiecki, A., & Rath, M. (2013). Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines. International Journal of Oncology, 43, 39-49. https://doi.org/10.3892/ijo.2013.1934
MLA
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines". International Journal of Oncology 43.1 (2013): 39-49.
Chicago
Roomi, M. W., Kalinovsky, T., Niedzwiecki, A., Rath, M."Modulation of u-PA, MMPs and their inhibitors by a novel nutrient mixture in adult human sarcoma cell lines". International Journal of Oncology 43, no. 1 (2013): 39-49. https://doi.org/10.3892/ijo.2013.1934
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