Spheroid culture of LuCaP 147 as an authentic preclinical model of prostate cancer subtype with SPOP mutation and hypermutator phenotype

• We established and characterized spheroid cultures of LuCaP 147 xenografts, models of advanced prostate cancer.
• LuCaP 147 cultures faithfully retained the characteristics of the original xenograft.
• We demonstrated capabilities for high-throughput drug screening using LuCaP 147 cultures.
• LuCaP 147 cultures formed tumors when re-introduced into mice.
• LuCaP 147 cultures provided an authentic in vitro preclinical model with a hypermutator phenotype and an SPOP mutation.

LuCaP serially transplantable xenografts are valuable preclinical models of locally advanced or metastatic prostate cancer. For the first time, we recently succeeded in establishing and serially passaging spheroid cultures of several LuCaP xenografts. Here, we characterized in depth the molecular and cellular phenotype of LuCaP 147 cultures and found faithful retention of the characteristics of the original xenograft, including immunophenotype, genetic fidelity, gene expression profile and responsiveness to androgen. Furthermore, we demonstrated capabilities for high-throughput drug screening and that anti-cancer agents induced cell cycle arrest and apoptosis in spheroid cultures. Finally, we showed that cells formed tumors when re-introduced into mice, providing an authentic in vitro–in vivo preclinical model of a subtype of prostate cancer with a hypermutator phenotype and an SPOP mutation.