TMOD-27. A NOVEL SET OF PATIENT-DERIVED ORTHOTOPIC XENOGRAFT (PDOX) MODELS OF PRIMARY AND RECURRENT INTRACRANIAL MENINGIOMA

Abstract

AbstractBACKGROUNDMeningioma is the most common brain tumors in adults. Cranial-base meningioma are difficult to achieve complete resection while others exhibit progression and aggressive profiles characterized by high recurrence rates and resistance to standard treatment. The lack of clinically relevant animal models is blocking the development of novel therapies. Here, we report our establishment of orthotopic xenograft mouse models and in vitro culture systems from surgical specimens of primary and recurrent meningiomas.METHODS6 primary surgical samples and 4 recurrent samples were obtained from meningioma patients. Tumor tissues were dissociated into single cells and directly implanted into right cranial base of NOD/SCID mice (1x105 cells/mouse). Primary cultures were initiated in serum-free and traditional FBS-based media. Tumor growth was monitored by small animal MRI. Pathologic features of the PDOX models and the matched patient tumors were compared with standard H&E and immunohistochemical staining.RESULTSThree of the 10 tumors were not tumorigenic, and xenograft tumor formation from 5 additional samples is pending. Growth of intracranial (cranial base) xenograft was confirmed in two samples derived from the same patient diagnosed as atypical meningioma (K029MEN) and progressed as anaplastic meningioma at recurrence (K037MEN). These PDOX have since been serially subtransplanted in mouse brains for generation 2. The xenograft tumors replicated histopathological features (invasion, high proliferation and increased microvessel density) of their parental tumors. In vitro growth of K029MEN and K037MEN as neurospheres and monolayer were maintained for passaging for 10 times. Additionally, cells from K030MEN (WHO grade I meningioma) has been passaged as monolayer for more than 30 times.CONCLUSIONA novel set of meningioma PDOX models derived from matching primary and recurrent tumor was established. The xenograft tumors replicated the histopathological of the original patient tumors, providing the opportunities to understand the biology of meningiomas and to conduct preclinical drug testing.