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Molecular characterization of an animal model of acromegaly induced by implantation of GC somatotroph tumor cell line

AuthorsSoto, Alfonso; Martín-Rodríguez, Juan Francisco; Venegas Moreno, Eva; Balcerzyk, Marcin ; Leal Cerro, Alfonso ; Cano González, David A.
Issue Date2014
CitationICN 2014
AbstractSubcutaneous implantation of GH-producing GC cells in female Wisth-Furth rats results in acromegalic phenotype (i.e. gigantism, visceromegaly, etc.). This animal model of acromegaly has been known for almost two decades and largely used to study the effects of chronic GH exposure on target tissues. However, little is known about the kinetics of tumor cell growth and information at the molecular level is scarce. In the current work Immunochemistry, molecular biology and imaging techniques were used to analyze in detail this animal model of acromegaly. GC cells (1 X 107) were injected sc into the flank of 7-week-old female rats. Control rats were injected sc with saline. Animals were weighed weekly. Tumors became palpable 2–3 weeks after implantation. For in vivo assessment of tumor growth and metabolism, microPET scans with 18F-FDG and [11C]Met were conducted at 1, 2, 4 and 8 weeks after implantation. After 20 weeks all animals were sacrificed and tumor samples were collected for further analysis. Immunohistochemical and quantitative real-time PCR analysis was conducted on tumor samples. A 1.5-2 fold increase in glucose uptake and [11C]Met accumulation was localized in the site of injection at 1 week after implantation, as compared to saline-treated rats. Highest peaks of these radiotracers at this site were found at 2 weeks after implantation. At 4 weeks, microPET scans clearly revealed evidence of tumor necrosis. Resected tumors were found to be exclusively GH-producing cells with no evidence of activation of other pituitary hormones. Analysis of somatostatin receptor expression revealed that sst2 was highly expressed followed by sst1. sst3 and sst5 were virtually absent in all samples analyzed. GHR and GHRHR were also present in the experimental tumors. Tumor cells displayed marked b-catenin and N-cadherin levels, showing a similar pattern to that found in normal pituitary, a finding consistent with the low metastastic potential of the somatotroph tumors. Interestingly, tumor cells expressed Sox2 and Sox9, two markers of pituitary progenitor cells. Altogether, our results show molecular similarities between GC-implanted tumors and human somatotroph adenomas. Thus, subcutaneous injection of GC cells might be a useful model to study the mechanisms of somatotroph adenoma tumorigenesis as well as to evaluate compounds for in vivo antitumoral activity.
DescriptionResumen del póster presentado al "8th International Congress of Neuroendocrinology" celebrado en Sydney (Australia) del 17 al 20 de agosto de 2014.-- et al.
Appears in Collections:(CNA) Comunicaciones congresos
(IBIS) Comunicaciones congresos
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