Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. In order to screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. Experimental Design: We initiated spheroids with primary ALDH+ CD133+ ovarian cancer stem cells (OvCSCs) from different patient samples, and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immune-deficient mice. Drug responses to cisplatin and ALDH targeting compound or JAK2 inhibitor determined if the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor re-emergence in a personalized manner. Results: OvCSC spheroids from different patients exhibited varying, and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with one single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to Cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression while those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH+ cells. Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro, and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.
http://ift.tt/2uRtqVj
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου