CAPC negatively regulates NF-κB activation and suppresses tumor growth and metastasis

Abstract

CAPC, also known as LRRC26, is expressed in normal prostate and salivary gland. We developed a monoclonal antibody to CAPC and used it to characterize the protein and study its function. CAPC protein was detected in normal prostate and salivary gland, in several human breast cancer cell lines and in the prostate cancer cell line LNCaP. Knock down of CAPC by siRNA in LNCaP cells enhanced anchorage-independent growth in soft agar. Conversely, over-expression of CAPC in MDA-231 breast cancer cells and the A431 epidermoid cancer cells inhibited growth in soft agar and tumorigenesis in nude mice, and suppressed metastasis of MDA-231 cells to the lung. Over-expression of CAPC down-regulated NF-κB activity and its target genes including GM-CSF (CSF2), CXCL1, IL8 and LTB1. It also suppressed genes encoding the serine protease mesotrypsin (PRSS3) and Cystatin SN (CST1). CAPC expressing tumors showed a decrease in the number of proliferating cells and a large increase in extracellular matrix. The role of CAPC in the suppression of tumor growth and metastasis may be through its alteration of the tumor microenvironment.