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Article

Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling

  • Authors:
    • Zheng Huang
    • Yanke Huang
    • Hongtao He
    • Jiangdong Ni
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Child Health Division, Shenzhen Nanshan District Mother‑Child Hospital, Shenzhen, Guangdong 518021, P.R. China
  • Pages: 3916-3922
    |
    Published online on: May 27, 2015
       https://doi.org/10.3892/mmr.2015.3859
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Abstract

Osteosarcoma (OS) is the most common type of primary bone malignancy. The use of multiagent, intensive chemotherapy has markedly improved the long‑term survival rate of patients with OS. However, chemoresistance continues to be the principal reason for poor survival and disease recurrence in patients with OS. Innate or acquired resistance to cisplatin, which is one of the most effective drugs against OS, is common. Understanding the molecular basis underlying cisplatin chemoresistance in OS cells may serve as a basis for the identification of novel therapeutic targets and biomarkers. High expression levels of podocalyxin (PCX) have been shown to be correlated with poor outcome in various types of cancer. A recent study suggested that PCX may contribute to cancer chemoresistance. The present study aimed to explore the role of PCX in OS by determining its effects on cisplatin chemoresistance in OS cells. Stable overexpression and knockdown of PCX were performed in MG‑63 and U2OS human OS cell lines. Overexpression of PCX in the two cell lines significantly increased the half maximal inhibitory concentration (IC50) of cisplatin, cell colony formation, phosphatidylinositide 3‑kinase (PI3K) activity and Akt phosphorylation at serine 473, and decreased cisplatin‑induced cell apoptosis. Furthermore, the effects of PCX were largely attenuated by treatment with the selective PI3K inhibitor BKM120. Conversely, knockdown of PCX expression markedly decreased the IC50 of cisplatin, cell colony formation, PI3K activity and Akt phosphorylation at serine 473, and increased cisplatin‑induced cell apoptosis. In conclusion, the present study was the first, to the best of our knowledge, to provide evidence that PCX promotes cisplatin chemoresistance in OS cells through a PI3K‑dependent mechanism. The results of the present study provided novel insight not only into the functional role of PCX in cancer, but also into the molecular mechanisms underlying OS chemoresistance.
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View References

1 

Ottaviani G and Jaffe N: The epidemiology of osteosarcoma. Cancer Treat Res. 152:3–13. 2009. View Article : Google Scholar

2 

Subbiah V and Kurzrock R: Phase 1 clinical trials for sarcomas: The cutting edge. Curr Opin Oncol. 23:352–360. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Fellenber J, Bernd L, Delling G, Witte D and Zahlten-Hinguranage A: Prognostic significance of drug-regulated genes in high-grade osteosarcoma. Mod Pathol. 20:1085–1094. 2007. View Article : Google Scholar

4 

Chou AJ and Gorlick R: Chemotherapy resistance in osteo-sarcoma: Current challenges and future directions. Expert Rev Anticancer Ther. 6:1075–1085. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Wang L, Jin F, Qin A, et al: Targeting Notch1 signaling pathway positively affects the sensitivity of osteosarcoma to cisplatin by regulating the expression and/or activity of Caspase family. Mol Cancer. 13:1392014. View Article : Google Scholar : PubMed/NCBI

6 

Abe S, Nishimoto Y, Isu K, Ishii T and Goto T; Japanese Musculoskeletal Oncology Group: Preoperative cisplatin for initial treatment of limb osteosarcoma: Its local effect and impact on prognosis. Cancer Chemother Pharmacol. 50:320–324. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Anninga JK, Gelderblom H, Fiocco M, et al: Chemotherapeutic adjuvant treatment for osteosarcoma: Where do we stand? Eur J Cancer. 47:2431–2445. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Uribe-Botero G, Russell WO, Sutow WW and Martin RG: Primary osteosarcoma of bone. Clinicopathologic investigation of 243 cases, with necropsy studies in 54. Am J Clin Pathol. 67:427–435. 1977.PubMed/NCBI

9 

Geller DS and Gorlick R: Osteosarcoma: A review of diagnosis, management and treatment strategies. Clin Adv Hematol Oncol. 8:705–718. 2010.

10 

Nielsen JS and McNagny KM: The role of podocalyxin in health and disease. J Am Soc Nephrol. 20:1669–1676. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Riccioni R, Calzolari A, Biffoni M, et al: Podocalyxin is expressed in normal and leukemic monocytes. Blood Cells Mol Dis. 37:218–225. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Kelley TW, Huntsman D, McNagny KM, Roskelley CD and Hsi ED: Podocalyxin: A marker of blasts in acute leukemia. Am J Clin Pathol. 124:134–142. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Yasuoka H, Tsujimoto M, Hirokawa M, et al: Podocalyxin expression in undifferentiated thyroid carcinomas. J Clin Pathol. 61:1228–1229. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Hsu YH, Lin WL, Hou YT, et al: Podocalyxin EBP50 ezrin molecular complex enhances the metastatic potential of renal cell carcinoma through recruiting Rac1 guanine nucleotide exchange factor ARHGEF7. Am J Pathol. 176:3050–3061. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Sizemore S, Cicek M, Sizemore N, Ng KP and Casey G: Podocalyxin increases the aggressive phenotype of breast and prostate cancer cells in vitro through its interaction with ezrin. Cancer Res. 67:6183–6191. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Somasiri A, Nielsen JS, Makretsov N, et al: Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression. Cancer Res. 64:5068–5073. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Wu H, Yang L, Liao D, Chen Y, Wang W and Fang J: Podocalyxin regulates astrocytoma cell invasion and survival against temozolomide. Exp Ther Med. 5:1025–1029. 2013.PubMed/NCBI

18 

Ding X, Zhang Z, Li S and Wang A: Combretastatin A4 phosphate induces programmed cell death in vascular endothelial cells. Oncol Res. 19:303–309. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Gu Y, Fan S, Xiong Y, et al: Cloning and functional characterization of TCRP1, a novel gene mediating resistance to cisplatin in an oral squamous cell carcinoma cell line. FEBS Lett. 585:881–887. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Cao CM, Zhang Y, Weisleder N, et al: MG53 constitutes a primary determinant of cardiac ischemic preconditioning. Circulation. 121:2565–2574. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Fos C, Salles A, Lang V, et al: ICOS ligation recruits the p50alpha PI3K regulatory subunit to the immunological synapse. J Immunol. 181:1969–1977. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Li B, Yang Y, Jiang S, Ni B, Chen K and Jiang L: Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma cell growth and migration through downregulation of the PI3K/AKT pathway. Int J Oncol. 41:1809–1819. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Liu ZL, Mao JH, Peng AF, et al: Inhibition of fatty acid synthase suppresses osteosarcoma cell invasion and migration via down-regulation of the PI3K/Akt signaling pathway in vitro. Mol Med Rep. 7:608–612. 2013.

24 

Zhao G, Cai C, Yang T, et al: MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 8:e539062013. View Article : Google Scholar : PubMed/NCBI

25 

Wang TF, Wang H, Peng AF, et al: Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro. Biochem Biophys Res Commun. 440:229–234. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Fellenberg J, Kunz P, Sähr H and Depeweg D: Overexpression of inosine 5′-monophosphate dehydrogenase type II mediates chemo-resistance to human osteosarcoma cells. PLoS One. 5:e121792010. View Article : Google Scholar

27 

Janeway KA and Grier HE: Sequelae of osteosarcoma medical therapy: A review of rare acute toxicities and late effects. Lancet Oncol. 11:670–678. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Bruheim S, Xi Y, Ju J and Fodstad O: Gene expression profiles classify human osteosarcoma xenografts according to sensitivity to doxorubicin, cisplatin and ifosfamide. Clin Cancer Res. 15:7161–7169. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Yasuoka H, Tsujimoto M, Inagaki M, et al: Clinicopathological significance of podocalyxin and phosphorylated ezrin in uterine endometrioid adenocarcinoma. J Clin Pathol. 65:399–402. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Larsson A, Johansson ME, Wangefjord S, et al: Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer. Br J Cancer. 105:666–672. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Somasiri A, Nielsen JS, Makretsov N, et al: Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression. Cancer Res. 64:5068–5073. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Liu M, Wang J, Huang H, et al: miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma. Biochem Biophys Res Commun. 441:364–370. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Tsai HC, Huang CY, Su HL and Tang CH: CCN2 enhances resistance to cisplatin-mediating cell apoptosis in human osteo-sarcoma. PLoS One. 9:e901592014. View Article : Google Scholar

34 

Rosenberg B, Vancamp L, Trosko JE and Mansour VH: Platinum compounds: A new class of potent antitumour agents. Nature. 222:385–386. 1969. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Huang Z, Huang Y, He H and Ni J: Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling. Mol Med Rep 12: 3916-3922, 2015.
APA
Huang, Z., Huang, Y., He, H., & Ni, J. (2015). Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling. Molecular Medicine Reports, 12, 3916-3922. https://doi.org/10.3892/mmr.2015.3859
MLA
Huang, Z., Huang, Y., He, H., Ni, J."Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling". Molecular Medicine Reports 12.3 (2015): 3916-3922.
Chicago
Huang, Z., Huang, Y., He, H., Ni, J."Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling". Molecular Medicine Reports 12, no. 3 (2015): 3916-3922. https://doi.org/10.3892/mmr.2015.3859
Copy and paste a formatted citation
x
Spandidos Publications style
Huang Z, Huang Y, He H and Ni J: Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling. Mol Med Rep 12: 3916-3922, 2015.
APA
Huang, Z., Huang, Y., He, H., & Ni, J. (2015). Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling. Molecular Medicine Reports, 12, 3916-3922. https://doi.org/10.3892/mmr.2015.3859
MLA
Huang, Z., Huang, Y., He, H., Ni, J."Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling". Molecular Medicine Reports 12.3 (2015): 3916-3922.
Chicago
Huang, Z., Huang, Y., He, H., Ni, J."Podocalyxin promotes cisplatin chemoresistance in osteosarcoma cells through phosphatidylinositide 3‑kinase signaling". Molecular Medicine Reports 12, no. 3 (2015): 3916-3922. https://doi.org/10.3892/mmr.2015.3859
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