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The role of nitric oxide synthases and nitrotyrosine in retinoblastoma

  1. Mohan Adithi M.Sc.,
  2. Venkatesan Nalini M.Sc.,
  3. Subramanian Krishnakumar M.D.†,*

Article first published online: 7 MAR 2005

DOI: 10.1002/cncr.20961

Issue

Cancer

Cancer

Volume 103, Issue 8, pages 1701–1711, 15 April 2005

Additional Information

How to Cite

Adithi, M., Nalini, V. and Krishnakumar, S. (2005), The role of nitric oxide synthases and nitrotyrosine in retinoblastoma. Cancer, 103: 1701–1711. doi: 10.1002/cncr.20961

Author Information

  1. Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Chennai, India

  1. †

    Fax: (011) 91 04428254180

*Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006, Tamil Nadu, India

Publication History

  1. Issue published online: 4 APR 2005
  2. Article first published online: 7 MAR 2005
  3. Manuscript Accepted: 16 DEC 2004
  4. Manuscript Revised: 27 NOV 2004
  5. Manuscript Received: 2 JUN 2004

Funded by

  • Indian Council for Medical Research. Grant Numbers: reference 5/4/6/6/2003-2004-NCD-II, Iris code 2003-000810

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Keywords:

  • endothelial nitric oxide synthase;
  • inducible nitric oxide synthase;
  • retinoblastoma;
  • immunohistochemistry;
  • invasion

Expression levels of the endothelial and inducible isoforms of nitric oxide synthase (eNOS and iNOS, respectively) and nitrotyrosine (NT) were studied in retinoblastoma and were correlated with tumor aggressiveness. Invasive retinoblastomas showed increased immunoreactivity for iNOS and NT. The data suggested that the expression of these molecules may be an essential functional aspect of retinoblastoma cells, perhaps in cell growth or survival. iNOS inhibition may represent an alternative treatment strategy for patients with advanced and resistant retinoblastoma.

Abstract

BACKGROUND

To investigate the potential involvement of the nitric oxide (NO) pathway in retinoblastoma, the authors correlated immunoreactivity for endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine (NT) with the degree of tumor invasiveness in retinoblastoma.

METHODS

eNOS, iNOS, and NT reactivity was evaluated by immunohistochemistry in 34 archival retinoblastoma specimens and in a human Y79 retinoblastoma cell line. The tumors were divided into 2 groups: Group A tumors (n = 17 tumors) with no invasion and Group B tumors (n = 17 tumors) with invasion of the choroid, optic nerve, and/or orbit. The expression levels of eNOS, iNOS, and NT were correlated with invasiveness of the tumors.

RESULTS

In Group A tumors (n = 17 tumors) without invasion, eNOS was positive in 17 of 17 tumors (100%), iNOS was positive in 14 of 17 tumors (82%), and NT was positive in 17 of 17 tumors (100%). In Group B tumors (n = 17 tumors) with invasion, eNOS was positive in 17 of 17 tumors (100%), iNOS was positive in 16 of 17 tumors (94%), and NT was positive in 17 of 17 tumors (100%). The invasive cohort showed significantly higher expression of iNOS (P < 0.0001) and NT (P < 0.020) compared with the noninvasive cohort. Y79 cells also expressed eNOS, iNOS, and NT; and nonneoplastic retina was positive for eNOS, iNOS, and NT.

CONCLUSIONS

Taken together, the results suggested that retinoblastomas can produce NO. The roles of NO in the biology of retinoblastoma and in the prognosis for patients with retinoblastoma remain to be established. Cancer 2005. © 2005 American Cancer Society.

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