Cryoablative response of prostate cancer cells is influenced by androgen receptor expression.
OBJECTIVE
To investigate in prostate cancer cells the consequences of androgen-insensitivity (AI) development on the cellular and molecular responses to freezing, as a challenge in prostate cancer treatment occurs when the androgen-sensitive (AS) phenotype switches to an AI phenotype, the latter of which is often refractory to many therapies.


METHODS
PC-3 (AI) and LNCaP (AS) were each genetically altered to express the opposite phenotype and subjected to an in vitro freezing model. Viability, caspase inhibitor and Western blot studies were used to determine the basis of the differential responses of AI and AS cells.


RESULTS
LNCaP high-passage cells, formed by repeated passage of LNCaP (AS) cells, were AI and showed a phenotypic shift to freeze resistance matching the freeze response of PC-3 cells (AI). While stably transfected androgen receptor (AR)-transfected cells (PC-3 AR) had a freezing sensitivity similar to that of the LNCaP (AS) cell line. Importantly, AI cell lines survived and recovered from freezing exposure to temperatures as low as -40 degrees C whereas AS cell lines did not. Caspase inhibition studies and related fluorescent probes showed an elevated level of apoptotic involvement in both AS cell lines after freezing compared with their AI counterparts. Western blot analysis showed that AR expression was modified after exposure to freezing.


CONCLUSIONS
This study suggests that AS cancers may be far more sensitive to a freezing insult and this might be linked to elevated apoptosis and caspase activity. As such, cryoablation may prove most effective in cancer cells that have not yet progressed to a more resistant AI phenotype, but both generic variants can be fully ablated at sufficiently low temperatures.
Klossner
Daniel P
DP
Institute of Biomedical Technology, SUNY, Binghamton, NY 13902, USA.
Baust
John M
JM
VanBuskirk
Robert G
RG
Gage
Andrew A
AA
Baust
John G
JG
D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003452:Cryosurgery / Q000379:methods*; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011944:Receptors, Androgen / Q000378:metabolism*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D011944:Receptors, Androgen