Upregulation of sodium iodide symporter (NIS) protein expression by an innate immunity component: Promising potential for targeting radiosensitive retinoblastoma
Authors: Narinderbir Singh
Subramanium Krishnakumar
Jagat Rakesh Kanwar
Jaisy Samuel
Rupinder Kaur Kanwar
Journal: Experimental Eye Research (2015)
Discipline: CLINICAL MEDICINE
Keywords: Bovine lactoferrin; Enhanced expression; Lactoferrin receptors; Retinoblastoma; Sodium iodide symporter.
Affiliations: Nanomedicine - Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular & Medical Research, Faculty of Health, Deakin University, Geelong, Victoria, Australia; Department of Nanobiotechnology, Kamalanayan Bajaj Research Institute, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai 600006, India., Nanomedicine - Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular & Medical Research, Faculty of Health, Deakin University, Geelong, Victoria, Australia., Department of Nanobiotechnology, Kamalanayan Bajaj Research Institute, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai 600006, India; L & T Ocular Pathology Department, Kamalanayan Bajaj Research Institute, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai 600006, India. Electronic address: ., Nanomedicine - Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular & Medical Research, Faculty of Health, Deakin University, Geelong, Victoria, Australia. Electronic address: .

Abstract:  Retinoblastoma (RB), a malignant tumour of the eye arising from developing retina, is the most frequent primary intraocular malignancy of childhood. Its primary management with chemotherapy involves combination regimen of etoposide, vincristine and carboplatin and intra vitreal chemotherapy using melphalan when vitreous seeds develop. Radiotherapy is another effective mode in treating RB. We recently explored the notion if radiotherapy in RB can be mediated via Sodium Iodide Symporter (NIS), an intrinsic membrane glycoprotein which is a key regulator of iodide access to thyroid gland. Its expression has been exploited successfully for diagnostic imaging and molecular radionuclide-based therapy of thyroid cancer. We determined that NIS is expressed endogenously in RB tumour tissues, and in retinoblastoma cell lines Y79 and Weri-Rb-1, and therefore made an attempt to enhance the endogenously low expression of NIS protein in both Y79 and Weri-Rb-1 cells. Here we report about the potential of bovine lactoferrin (bLf) which is a known chemo preventive and emerging safe anti-cancer bio drug, as well as a natural transcriptional activator of genes, to enhance the endogenous expression of NIS in Y79 and Weri-Rb-1 cells. Real time PCR revealed that both cell lines express mRNA of lactoferrin receptors while flow cytometry and confocal microscopy showed the cells efficiently internalize bLf which upregulates NIS expression. These findings highlight an important step that could be taken towards the development of less harmful approaches for the treatment of RB by employing natural supplement bLf (with its clinically proven safe profile), and warrants further studies in future, focussing on enhancing NIS expression in RB cells and NIS functional assays in these cells. 

Retracted: No

PubPeer comments:
 There is an instance of image duplication in this paper. In Figure 1C the same histogram has been used 3 times. Twice in a control group and one in a treatment group. The histograms have been resized but they are clearly identical. See the histograms in the green boxes in the attached image. It may be an error whereby the two top left hand histograms have been placed in the wrong column. Strange the journal reviewers or the journal editors didn t pick this up. ![file] ,