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

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 303-321-Cancer in Endocrine Tissues
Bench to Bedside
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-317
Juan Francisco Martin-Rodriguez*1, Rocío Leal-Campanario2, Alfonso Soto-Moreno3, Eva Venegas-Moreno1, Laura Fernandez-Maza4, Marcin Balcerzyk5, Justo Pastor Castano6, Raul M. Luque6, David A Cano1 and Alfonso Leal-Cerro3
1Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla & Endocrinology and Nutrition Unit, Virgen del Rocio, Seville, Spain, 2Division of Neurosciences, Pablo de Olavide University, Seville, Spain, 3Instituto de Biomedicina de Sevilla (IBiS), Consejo Superior de Investigaciones Científicas, Endocrinology Unit of Virgen del Rocío University Hospital, University of Seville, Sevilla, Spain, 4Cyclotron Unit, The National Center of Accelerators (CNA), University of Seville, Seville, Spain, 5Cyclotron Unit, The National Center of Accelerators (CNA), University of Seville, seville, Spain, 6University of Córdoba, Reina Sofía University Hospital, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC); CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Cordoba, Spain
Subcutaneous 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.

Nothing to Disclose: JFM, RL, AS, EV, LF, MB, JPC, RML, DAC, AL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Junta de Andalucia (CTS-444); Pfizer España; Consejería de Salud y Bienestar Social (PI-0302-2012); UGEN HUVR