Cryoablative response of prostate cancer cells is influenced by androgen receptor expression

• Published in: BJU international Vol. 101; no. 10; pp. 1310 - 1316
• Main Authors: Klossner, Daniel P., Baust, John M., VanBuskirk, Robert G., Gage, Andrew A., Baust, John G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2008; Blackwell
• Subjects: androgen sensitivity; Apoptosis; Biological and medical sciences; Blotting, Western; caspase; Cell Line, Tumor; cryosurgery; Cryosurgery - methods; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - surgery; Nephrology. Urinary tract diseases; Phenotype; prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Receptors, Androgen - metabolism; Sensitivity and Specificity; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Nephrology; Prostate disease; Cysteine endopeptidases; Urology; Surgery; Male genital diseases; Tumor cell; Urinary system disease; Androgen; Cryosurgery; Enzyme; Caspase; Malignant tumor; androgen sensitivity; Peptidases; Sensitivity; Treatment; Cell death; Androgen receptor; Hydrolases; Sex steroid hormone; Prostate cancer; Cancer; Apoptosis; Hormonal receptor
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2008.07499.x

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. MATERIALS AND 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 °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. CONCLUSION 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.