Characterization of the first established  large cell neuroendocrine prostate cancer cell line
Prostate cancer is the fourth most common cancer worldwide and the second most common cancer among men. Despite the high incidence rate, in vitro research of prostate cancer has been limited to fewer than ten commonly available cell lines. The limited availability of disease representative cell models is a widely acknowledged challenge in translational prostate cancer research. Moreover, for specific molecular and genetic subtypes no representative cell lines exist. Large cell neuroendocrine prostate cancer is a rare and aggressive entity of prostate cancer. Due to a lack of validated markers for diagnosis, large cell neuroendocrine prostate cancer is generally under-recognized, and the therapeutic implications remain poorly understood. Here, we describe the establishment of the first reported spontaneously immortal large cell neuroendocrine prostate cancer cell line; MISB114, characterized by aggressive neuroendocrine prostate cancer associated molecular features including high Neuronatin expression, AR independency and complete inactivation of TP53 and RB1. High-throughput drug screening studies indicate a drug sensitivity profile reflecting the dual TP53/RB1 loss associated with elevated replication stress and sensitivity to DNA repair targeting. MISB114 cell line provides an invaluable novel model for the study of pathogenesis, molecular characteristics and drug sensitivity of large cell neuroendocrine prostate cancer.
Prostate cancer is the fourth most common cancer worldwide and the second most common cancer among men. Despite the high incidence rate, in vitro research of prostate cancer has been limited to fewer than ten commonly available cell lines. The limited availability of disease representative cell models is a widely acknowledged challenge in translational prostate cancer research. Moreover, for specific molecular and genetic subtypes no representative cell lines exist. Large cell neuroendocrine prostate cancer is a rare and aggressive entity of prostate cancer. Due to a lack of validated markers for diagnosis, large cell neuroendocrine prostate cancer is generally under-recognized, and the therapeutic implications remain poorly understood. Here, we describe the establishment of the first reported spontaneously immortal large cell neuroendocrine prostate cancer cell line; MISB114, characterized by aggressive neuroendocrine prostate cancer associated molecular features including high Neuronatin expression, AR independency and complete inactivation of TP53 and RB1. High-throughput drug screening studies indicate a drug sensitivity profile reflecting the dual TP53/RB1 loss associated with elevated replication stress and sensitivity to DNA repair targeting. MISB114 cell line provides an invaluable novel model for the study of pathogenesis, molecular characteristics and drug sensitivity of large cell neuroendocrine prostate cancer.
Misvik Biology Ltd