Bede van Schaijik1, Swee T Tan2,3, Reginald W Marsh1,4, Tinte Itinteang1. 1. Gillies McIndoe Research Institute, Wellington, New Zealand. 2. Gillies McIndoe Research Institute, Wellington, New Zealand. swee.tan@gmri.org.nz. 3. Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand. swee.tan@gmri.org.nz. 4. University of Auckland, Auckland, New Zealand.
Abstract
BACKGROUND: Propranolol is the preferred treatment for problematic proliferating infantile hemangioma (IH) by targeting the renin-angiotensin system (RAS) expressed by IH endothelium. (Pro)renin receptor (PRR) is a major component of the RAS associated with the canonical wnt signaling pathway. We proposed that activation of PRR by renin causes proliferation of IH. METHODS: The expression of PRR in IH tissue samples was investigated using immunohistochemical (IHC) staining and NanoString analysis. NanoString analysis was also used to confirm transcriptional expression of PRR in CD34-sorted proliferating IH-derived primary cell lines. MTT assay was utilized to determine the effect of exogenous renin on the number of viable IH cells. RT-qPCR was used to determine the effect of renin on the stem cell gene expression. RESULTS: NanoString analysis and IHC staining confirmed transcriptional and translational expression of PRR, which was localized to the non-endothelial and the endothelial IH cell populations. MTT assay demonstrated an increased number of viable IH cells by administration of renin and the effect was negated by the wnt receptor blocker dickkopf-1. CONCLUSION: Our results present a model for renin-induced increased proliferation of IH cells through PRR acting via the wnt signaling pathway, which may account for accumulation of cells in IH during the proliferative phase of the tumor.
BACKGROUND: Propranolol is the preferred treatment for problematic proliferating infantile hemangioma (IH) by targeting the renin-angiotensin system (RAS) expressed by IH endothelium. (Pro)renin receptor (PRR) is a major component of the RAS associated with the canonical wnt signaling pathway. We proposed that activation of PRR by renin causes proliferation of IH. METHODS: The expression of PRR in IH tissue samples was investigated using immunohistochemical (IHC) staining and NanoString analysis. NanoString analysis was also used to confirm transcriptional expression of PRR in CD34-sorted proliferating IH-derived primary cell lines. MTT assay was utilized to determine the effect of exogenous renin on the number of viable IH cells. RT-qPCR was used to determine the effect of renin on the stem cell gene expression. RESULTS: NanoString analysis and IHC staining confirmed transcriptional and translational expression of PRR, which was localized to the non-endothelial and the endothelial IH cell populations. MTT assay demonstrated an increased number of viable IH cells by administration of renin and the effect was negated by the wnt receptor blocker dickkopf-1. CONCLUSION: Our results present a model for renin-induced increased proliferation of IH cells through PRR acting via the wnt signaling pathway, which may account for accumulation of cells in IH during the proliferative phase of the tumor.
Authors: Cherise Es Tan; Tinte Itinteang; Philip Leadbitter; Reginald Marsh; Swee T Tan Journal: J Paediatr Child Health Date: 2014-09-03 Impact factor: 1.954
Authors: Zia A Khan; Elisa Boscolo; Arnaud Picard; Sarah Psutka; Juan M Melero-Martin; Tatianna C Bartch; John B Mulliken; Joyce Bischoff Journal: J Clin Invest Date: 2008-07 Impact factor: 14.808