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Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis

  • Authors:
    • Antonis Papoutsidakis
    • Eirini Maria Giatagana
    • Aikaterini Berdiaki
    • Ioanna Spyridaki
    • Demetrios A. Spandidos
    • Aristidis Tsatsakis
    • George N. Tzanakakis
    • Dragana Nikitovic
  • View Affiliations / Copyright

    Affiliations: Laboratory of Anatomy‑Histology‑Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece, Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece, Laboratory of Toxicology, School of Medicine, University of Crete, 71003 Heraklion, Greece
  • Pages: 791-803
    |
    Published online on: July 6, 2020
       https://doi.org/10.3892/ijo.2020.5094
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Abstract

Chondrosarcoma is a malignant bone tumor characterized by the production of a modified cartilage‑type extracellular matrix (ECM). In the present study, the expression levels of the small leucine‑rich proteoglycans (SLRPs), decorin, biglycan and lumican, were examined in the HTB94 human chondrosarcoma cell line. HTB94 cells were found to express and secrete the 3 SLRP members. RT‑qPCR and western blot analysis demonstrated that lumican was the most abundantly secreted SLRP, whereas decorin and biglycan expression levels were low. The utilization of short interfering RNA specific for the decorin, biglycan, and lumican genes resulted in the efficient downregulation of the respective mRNA levels (P≤0.001). The growth of the HTB94 cells was stimulated by lumican (P≤0.001), whereas their migration and adhesion were not affected (P=NS). By contrast, these cellular functions were not sensitive to a decrease in low endogenous levels of decorin and biglycan. Lumicandeficiency significantly inhibited both basal and insulin‑like growth factor I (IGF‑I)‑induced HTB94 cell growth (P≤0.001 andP≤0.01, respectively). These effects were executed through the insulin‑like growth factor I receptor (IGF‑IR), whose activation was markedly attenuated (P≤0.01) in lumican‑deficient HTB94 cells. The downregulation of lumican induced the substantial inhibition of extracellular regulated kinase (ERK1/2) activation (P≤ 0.01), indicating that ERK1/2 is a necessary component of lumican/IGF‑IR‑mediated HTB94 cell proliferation. Moreover, the lumican‑deficient cells exhibit increased mRNA levels of p53 (P≤0.05), suggesting that lumican facilitates HTB94 cell growth through an IGF‑IR/ERK1/2/p53 signaling cascade. On the whole, the findings of the present study demonstrate that endogenous lumican is a novel regulator of HTB94 cell growth.
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Copy and paste a formatted citation
Spandidos Publications style
Papoutsidakis A, Giatagana EM, Berdiaki A, Spyridaki I, Spandidos DA, Tsatsakis A, Tzanakakis GN and Nikitovic D: Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis. Int J Oncol 57: 791-803, 2020.
APA
Papoutsidakis, A., Giatagana, E.M., Berdiaki, A., Spyridaki, I., Spandidos, D.A., Tsatsakis, A. ... Nikitovic, D. (2020). Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis. International Journal of Oncology, 57, 791-803. https://doi.org/10.3892/ijo.2020.5094
MLA
Papoutsidakis, A., Giatagana, E. M., Berdiaki, A., Spyridaki, I., Spandidos, D. A., Tsatsakis, A., Tzanakakis, G. N., Nikitovic, D."Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis". International Journal of Oncology 57.3 (2020): 791-803.
Chicago
Papoutsidakis, A., Giatagana, E. M., Berdiaki, A., Spyridaki, I., Spandidos, D. A., Tsatsakis, A., Tzanakakis, G. N., Nikitovic, D."Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis". International Journal of Oncology 57, no. 3 (2020): 791-803. https://doi.org/10.3892/ijo.2020.5094
Copy and paste a formatted citation
x
Spandidos Publications style
Papoutsidakis A, Giatagana EM, Berdiaki A, Spyridaki I, Spandidos DA, Tsatsakis A, Tzanakakis GN and Nikitovic D: Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis. Int J Oncol 57: 791-803, 2020.
APA
Papoutsidakis, A., Giatagana, E.M., Berdiaki, A., Spyridaki, I., Spandidos, D.A., Tsatsakis, A. ... Nikitovic, D. (2020). Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis. International Journal of Oncology, 57, 791-803. https://doi.org/10.3892/ijo.2020.5094
MLA
Papoutsidakis, A., Giatagana, E. M., Berdiaki, A., Spyridaki, I., Spandidos, D. A., Tsatsakis, A., Tzanakakis, G. N., Nikitovic, D."Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis". International Journal of Oncology 57.3 (2020): 791-803.
Chicago
Papoutsidakis, A., Giatagana, E. M., Berdiaki, A., Spyridaki, I., Spandidos, D. A., Tsatsakis, A., Tzanakakis, G. N., Nikitovic, D."Lumican mediates HTB94 chondrosarcoma cell growth via an IGF‑IR/Erk1/2 axis". International Journal of Oncology 57, no. 3 (2020): 791-803. https://doi.org/10.3892/ijo.2020.5094
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