Autologous spheroid culture: a screening tool for human brain tumour invasion

Spheroids are three-dimensional cell aggregates expressing histotypic organ isation in vitro comparable to tissue continuity in vivo. They can be prepa red from normal tissue and from tumour fragments. In the experiments presen ted here, dermal human spheroids and brain tumour spheroids are prepared fr om the same patient. The dermal tissue originates from the border of the in cision wound made to effect a stereotactic brain tumour biopsy. The tumour originates from a fragment of the collected stereotactic biopsy. The dermal fragment and the brain biopsy are explanted in vitro to form confluent mon olayers. At confluency, the dermal cells are transferred into small Erlenme yer flasks and rotated at 37 degreesC for 1-2 days and rotation mediated sp heroids are formed. Small flaps of the tumour monolayer are placed on a sem isolid non-adhesive substrate, reorganise and form agar overlay spheroids. After spheroid formation, a dermal spheroid is confronted with a brain tumo ur derived spheroid. The confronting pair, after adhering to each other, pr esent an invasion model in vitro. The dermal spheroid functions as the auto logous host for the brain tumour spheroid. Putative invasive cells present in the reaggregated brain spheroid will invade the dermal spheroid and dest roy it. If no invasive cells are present in the tumour derived spheroid no morphologic changes will be seen in the dermal spheroid; 24 tested brain bi opsy spheroids demonstrated a clear correlation between malignancy in situ and invasiveness in vitro. So it can be concluded that the autologous confr ontation of brain tumour derived spheroids with dermal spheroids derived fr om the patient has a predictive value concerning malignant evolution and mi mics the situation of the tumour in situ. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.