TRPV6 Calcium Channel Targeting by Antibodies Raised against Extracellular Epitopes Induces Prostate Cancer Cell...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• The Transient Receptor Potential Vanilloid 6 (TRPV6) calcium channel is frequently overexpressed in various cancers.
• Targeting TRPV6 in vivo is a developing strategy for effective anti-cancer therapies.

Purpose of the Study:

• To generate and characterize novel antibodies targeting extracellular epitopes of the TRPV6 channel.
• To evaluate the efficacy of these antibodies in reducing cancer cell survival and inducing apoptosis.

Main Methods:

• Generation of antibodies (rb79 and rb82) against specific TRPV6 extracellular epitopes.
• Assessment of TRPV6 channel activity and store-operated calcium entry in LNCaP cells.
• Evaluation of cell survival, apoptosis (sub-G1 peak, TUNEL assay, Hoechst staining), and TRPV6 membrane expression.

Main Results:

• Antibodies rb79 and rb82 induced a biphasic TRPV6 channel activation and potentiated store-operated calcium entry in LNCaP cells.
• Both antibodies significantly reduced LNCaP cell survival in a dose-dependent manner, inducing apoptosis.
• No significant effects were observed in the PC3M cell line, indicating specificity.
• TUNEL-positive cells consistently showed TRPV6 membrane staining, unlike control antibody treatments.

Conclusions:

• Targeting the TRPV6 channel with antibodies rb79 and rb82 is a potent strategy for inducing cancer cell death.
• These antibodies demonstrate therapeutic potential for anti-cancer treatments, particularly in cancers with TRPV6 upregulation.