Subcutaneous implantation of GH-producing GC cells in female Wisth-Furth rats results in acromegalic phenotype. 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 characterize in detail this animal model of acromegaly and the tumors induced.
GC cells were injected sc into the flank of 7-week-old rats. Tumors became palpable 2–3 weeks after implantation. For in vivoassessment of tumor growth and metabolism, microPET scans with 18F-FDG and [11C]Met were conducted at 1, 2, and 4 after implantation. 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. Highest peaks of these radiotracers at this site were found at 2 weeks after implantation. At 4 weeks, microPET scans revealed evidence of tumor necrosis.
Immunohistochemical and qPCR analysis conducted on tumor samples confirmed the tumors to be composed exclusively of GH-producing cells with no evidence of activation of expression of other pituitary hormones. Analysis of somatostatin receptor expression revealed that sst2 was highly expressed followed by sst1. Tumor cells displayed marked beta-catenin and N-cadherin levels, showing a similar pattern to that found in human somatotroph adenomas, a finding consistent with the low metastastic potential of these 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 certain cellular/molecular aspects of somatotroph adenomas as well as to evaluate compounds for in vivo antitumoral activity.