975 ORTHOTOPIC TUMORGRAFTS DERIVED FROM MEN WITH LOCALIZED PROSTATE CANCER REFLECT INITIAL TUMOR PATHOLOGY – A NEW MODEL TO STUDY PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVES: Animal models that authentically reproduce tumor growth are still sparse in prostate cancer research for several reasons: Whilst orthotopic implantation is technically difficult, most models favor subcutaneous tumor growth that provides little information about natural tumor growth behaviour and tumor stroma interaction. Established prostate cancer cell lines as in vivo xenografts are not able to reflect the variety of tumor specific growth patterns and growth behaviour. Primary cell cultures are difficult to handle and an induction of orthotopic tumors has not been successful yet. Therefore, a tumorgraft model using tumor tissue from prostatectomy specimens was recently developed. METHODS: Balb/c mice were used to graft fresh prostate tumor tissue by surgical orthotopic implantation. Tissue implantation was performed at four inoculation sides in each animal and testosterone propionate was supplemented. Animals were tracked after 12, 16 and 20 weeks by means of 30MHz ultrasound to monitor tumor engraftment. Autopsy, histology and PSA measurements were used to confirm orthotopic tumors after 13, 21 and 28 weeks. RESULTS: To date, tumor implantation was performed in 17 mice. 3 animals were excluded due to early dead or repetitive loss of the testosterone pellet. After successful testosterone supplementation PSA measurement was possible in 12 of 14 mice (86%, range: 0,009 80ng/ml). So far, orthotopic tumor growth was histologically verified in 6 of 14 mice. Ultrasound seems feasible to detect tumors. Of interest, tumorgrafts maintain essential features of the original tumors as tumor growth pattern, PSA expression, androgen receptor expression and high proliferation using human Ki67 immunostaining. CONCLUSIONS: The tumorgrafts resembled histological properties of organ confined prostate cancer. Measurements of serum PSA and three-dimensional ultrasound were useful for monitoring of tumor engraftment and growth. Further studies like comparative genomic hybridization to genetically characterize tumorgrafts are necessary. Besides their role as a bank of tumor samples for repetitive in vitro studies, tumorgrafts display a new approach for an optimized in vivo model of prostate cancer and will allow further investigations on specific components of tumor initiation and progression, including the interactions of prostate cancer cells with the surrounding stroma. Whether this model is also applicable for metastatic progression needs to be further investigated.