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Article

The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma

  • Authors:
    • G. S. Sailaja
    • Praveen Bhoopathi
    • Bharathi Gorantla
    • Chandramu Chetty
    • Venkateswara Rao Gogineni
    • Kiran Kumar Velpula
    • Christopher S. Gondi
    • Jasti S. Rao
  • View Affiliations / Copyright

    Affiliations: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
  • Pages: 188-196
    |
    Published online on: October 24, 2012
       https://doi.org/10.3892/ijo.2012.1678
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Abstract

Our previous studies showed that overexpression of secreted protein acidic and rich in cysteine (SPARC) induced autophagy-mediated apoptosis in PNET cells. In the present study, we attempted to elucidate the molecular mechanisms and signaling cascades associated with SPARC overexpression in combination with radiation therapy that eventually leads to autophagy-mediated apoptosis in neuroblastoma. SPARC expression in SK-N-AS and NB-1691 cells demonstrated the activation of caspase 3, cleavage of PARP and induction of apoptosis. The experiments to unravel the mechanisms associated with autophagy-apoptosis illustrated that SPARC overexpression triggered endoplasmic reticulum (ER) stress and thereby unfolded protein response (UPR). This was apparent with the activation of stress receptors, inositol-requiring enzyme (IRE 1α), RNA-dependent protein kinase (PKR)-like ER kinase (PERK) and BiP. This study further demonstrated the induction of transcription factor CHOP as a result of IRE-JNK activation in response to increased SPARC levels. Inhibition of ER stress and JNK activation led to inhibition of autophagy-mediated apoptosis. Further, the apparent expression of ER stress molecules among the orthotopic tumors treated by SPARC overexpression plasmids substantiated our in vitro observations. Taken together, these results illustrate the critical role of ER stress in regulating autophagy-mediated apoptosis in SPARC-overexpressed neuroblastoma cells and radiation treatment.
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1. 

Maris JM and Matthay KK: Molecular biology of neuroblastoma. J Clin Oncol. 17:2264–2279. 1999.PubMed/NCBI

2. 

Smith MA, Seibel NL, Altekruse SF, et al: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol. 28:2625–2634. 2010. View Article : Google Scholar : PubMed/NCBI

3. 

Jennings RW, LaQuaglia MP, Leong K, Hendren WH and Adzick NS: Fetal neuroblastoma: prenatal diagnosis and natural history. J Pediatr Surg. 28:1168–1174. 1993. View Article : Google Scholar : PubMed/NCBI

4. 

Fulda S and Debatin KM: Apoptosis pathways in neuroblastoma therapy. Cancer Lett. 197:131–135. 2003. View Article : Google Scholar

5. 

Arnold SA and Brekken RA: SPARC: a matricellular regulator of tumorigenesis. J Cell Commun Signal. 3:255–273. 2009. View Article : Google Scholar : PubMed/NCBI

6. 

Mok SC, Chan WY, Wong KK, Muto MG and Berkowitz RS: SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells. Oncogene. 12:1895–1901. 1996.PubMed/NCBI

7. 

Sato N, Fukushima N, Maehara N, et al: SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene. 22:5021–5030. 2003. View Article : Google Scholar : PubMed/NCBI

8. 

Sova P, Feng Q, Geiss G, et al: Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis. Cancer Epidemiol Biomarkers Prev. 15:114–123. 2006. View Article : Google Scholar : PubMed/NCBI

9. 

Chen Y, Chen JC and Tseng SH: Effects of tetrandrine plus radiation on neuroblastoma cells. Anticancer Res. 29:3163–3171. 2009.PubMed/NCBI

10. 

Chen M, Hough AM and Lawrence TS: The role of p53 in gemcitabine-mediated cytotoxicity and radiosensitization. Cancer Chemother Pharmacol. 45:369–374. 2000. View Article : Google Scholar : PubMed/NCBI

11. 

Steel GG and Peckham MJ: Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys. 5:85–91. 1979. View Article : Google Scholar : PubMed/NCBI

12. 

Heck A: [Endoscopic operations spare the patient. Rapid rehabilitation, dispensing with large incisions, removal of appendix, gallbladder and esophagus]. Krankenpfl J. 29:148–149. 1991.(In German).

13. 

Bhoopathi P, Gondi CS, Gujrati M, Dinh DH and Lakka SS: SPARC mediates Src-induced disruption of actin cytoskeleton via inactivation of small GTPases Rho-Rac-Cdc42. Cell Signal. 23:1978–1987. 2011. View Article : Google Scholar : PubMed/NCBI

14. 

Bhoopathi P, Chetty C, Gujrati M, Dinh DH, Rao JS and Lakka SS: Cathepsin B facilitates autophagy mediated apoptosis in SPARC overexpressed primitive neuroectodermal tumor cells. Cell Death Differ. 17:1529–1539. 2010. View Article : Google Scholar

15. 

Hoyer-Hansen M and Jaattela M: Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ. 14:1576–1582. 2007. View Article : Google Scholar : PubMed/NCBI

16. 

Ding WX, Ni HM, Gao W, et al: Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival. J Biol Chem. 282:4702–4710. 2007. View Article : Google Scholar : PubMed/NCBI

17. 

Bhoopathi P, Chetty C, Gujrati M, Dinh DH, Rao JS and Lakka SS: The role of MMP-9 in the anti-angiogenic effect of secreted protein acidic and rich in cysteine. Br J Cancer. 102:530–540. 2010. View Article : Google Scholar : PubMed/NCBI

18. 

Mohanam S, Jasti SL, Kondraganti SR, et al: Stable transfection of urokinase-type plasminogen activator antisense construct modulates invasion of human glioblastoma cells. Clin Cancer Res. 7:2519–2526. 2001.PubMed/NCBI

19. 

Bhoopathi P, Chetty C, Kunigal S, Vanamala SK, Rao JS and Lakka SS: Blockade of tumor growth due to matrix metalloproteinase-9 inhibition is mediated by sequential activation of beta1-integrin, ERK, and NF-kappaB. J Biol Chem. 283:1545–1552. 2008. View Article : Google Scholar : PubMed/NCBI

20. 

Chetty C, Lakka SS, Bhoopathi P, Kunigal S, Geiss R and Rao JS: Tissue inhibitor of metalloproteinase 3 suppresses tumor angiogenesis in matrix metalloproteinase 2-down-regulated lung cancer. Cancer Res. 68:4736–4745. 2008. View Article : Google Scholar : PubMed/NCBI

21. 

Tivnan A, Tracey L, Buckley PG, Alcock LC, Davidoff AM and Stallings RL: MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC Cancer. 11:332011. View Article : Google Scholar : PubMed/NCBI

22. 

Ogata M, Hino S, Saito A, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar : PubMed/NCBI

23. 

Liu J and Lin A: Role of JNK activation in apoptosis: a double-edged sword. Cell Res. 15:36–42. 2005. View Article : Google Scholar : PubMed/NCBI

24. 

Hetz C: The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 13:89–102. 2012.PubMed/NCBI

25. 

Clark CJ and Sage EH: A prototypic matricellular protein in the tumor microenvironment - where there’s SPARC, there’s fire. J Cell Biochem. 104:721–732. 2008.PubMed/NCBI

26. 

Podhajcer OL, Benedetti L, Girotti MR, Prada F, Salvatierra E and Llera AS: The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev. 27:691–705. 2008. View Article : Google Scholar

27. 

Fulda S and Debatin KM: IFNgamma sensitizes for apoptosis by upregulating caspase-8 expression through the Stat1 pathway. Oncogene. 21:2295–2308. 2002. View Article : Google Scholar : PubMed/NCBI

28. 

Deniaud A, Sharaf el Dein O, Maillier E, Poncet D, Kroemer G, Lemaire C and Brenner C: Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene. 27:285–299. 2008. View Article : Google Scholar

29. 

Kuma A, Hatano M, Matsui M, et al: The role of autophagy during the early neonatal starvation period. Nature. 432:1032–1036. 2004. View Article : Google Scholar : PubMed/NCBI

30. 

Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP and Ron D: Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 287:664–666. 2000. View Article : Google Scholar : PubMed/NCBI

31. 

Lin JH, Li H, Zhang Y, Ron D and Walter P: Divergent effects of PERK and IRE1 signaling on cell viability. PLoS One. 4:e41702009. View Article : Google Scholar : PubMed/NCBI

32. 

Bertolotti A, Zhang Y, Hendershot LM, Harding HP and Ron D: Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2:326–332. 2000. View Article : Google Scholar : PubMed/NCBI

33. 

Zinszner H, Kuroda M, Wang X, et al: CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12:982–995. 1998. View Article : Google Scholar : PubMed/NCBI

34. 

Mah LY and Ryan KM: Autophagy and cancer. Cold Spring Harb Perspect Biol. 4:a0088212012.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sailaja GS, Bhoopathi P, Gorantla B, Chetty C, Gogineni VR, Velpula KK, Gondi CS and Rao JS: The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma. Int J Oncol 42: 188-196, 2013.
APA
Sailaja, G.S., Bhoopathi, P., Gorantla, B., Chetty, C., Gogineni, V.R., Velpula, K.K. ... Rao, J.S. (2013). The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma. International Journal of Oncology, 42, 188-196. https://doi.org/10.3892/ijo.2012.1678
MLA
Sailaja, G. S., Bhoopathi, P., Gorantla, B., Chetty, C., Gogineni, V. R., Velpula, K. K., Gondi, C. S., Rao, J. S."The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma". International Journal of Oncology 42.1 (2013): 188-196.
Chicago
Sailaja, G. S., Bhoopathi, P., Gorantla, B., Chetty, C., Gogineni, V. R., Velpula, K. K., Gondi, C. S., Rao, J. S."The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma". International Journal of Oncology 42, no. 1 (2013): 188-196. https://doi.org/10.3892/ijo.2012.1678
Copy and paste a formatted citation
x
Spandidos Publications style
Sailaja GS, Bhoopathi P, Gorantla B, Chetty C, Gogineni VR, Velpula KK, Gondi CS and Rao JS: The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma. Int J Oncol 42: 188-196, 2013.
APA
Sailaja, G.S., Bhoopathi, P., Gorantla, B., Chetty, C., Gogineni, V.R., Velpula, K.K. ... Rao, J.S. (2013). The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma. International Journal of Oncology, 42, 188-196. https://doi.org/10.3892/ijo.2012.1678
MLA
Sailaja, G. S., Bhoopathi, P., Gorantla, B., Chetty, C., Gogineni, V. R., Velpula, K. K., Gondi, C. S., Rao, J. S."The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma". International Journal of Oncology 42.1 (2013): 188-196.
Chicago
Sailaja, G. S., Bhoopathi, P., Gorantla, B., Chetty, C., Gogineni, V. R., Velpula, K. K., Gondi, C. S., Rao, J. S."The secreted protein acidic and rich in cysteine (SPARC) induces endoplasmic reticulum stress leading to autophagy-mediated apoptosis in neuroblastoma". International Journal of Oncology 42, no. 1 (2013): 188-196. https://doi.org/10.3892/ijo.2012.1678
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