title: Upregulation of sodium iodide symporter (NIS) protein expression by an innate immunity component: Promising potential for targeting radiosensitive retinoblastoma.
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.
authors.affiliation: 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.
authors.forename: Jaisy
authors.initials: J
authors.lastname: Samuel
authors.affiliation: Nanomedicine - Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular & Medical Research, Faculty of Health, Deakin University, Geelong, Victoria, Australia.
authors.forename: Narinderbir
authors.initials: N
authors.lastname: Singh
authors.affiliation: Nanomedicine - Laboratory of Immunology and Molecular Biomedical Research, School of Medicine, Centre for Molecular & Medical Research, Faculty of Health, Deakin University, Geelong, Victoria, Australia.
authors.forename: Jagat Rakesh
authors.initials: JR
authors.lastname: Kanwar
authors.affiliation: 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: drkrishnakumar_2000@yahoo.com.
authors.forename: Subramanium
authors.initials: S
authors.lastname: Krishnakumar
authors.affiliation: 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: rupinder.kanwar@deakin.edu.au.
authors.forename: Rupinder Kaur
authors.initials: RK
authors.lastname: Kanwar
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018613:Microscopy, Confocal; D012334:RNA, Neoplasm / Q000235:genetics*; D019572:Retinal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation; D000099209:Sodium-Iodide Symporters
chemical_list: D012334:RNA, Neoplasm; D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: Bovine lactoferrin; Enhanced expression; Lactoferrin receptors; Retinoblastoma; Sodium iodide symporter