Characterization of human cathelicidin antimicrobial protein (CAMP) in breast cancer

Abstract

Background: It is well-established that tumor associated macrophages (TAMs) play important role in breast cancer development. Accumulating evidence suggested that human cathelicidin antimicrobial protein (CAMP), which is mainly expressed in host defense cells such as macrophages, is crucial not only in combating microorganisms but also promoting tumor growth. Our study aims to elucidate the interaction of CAMP with TAMs in breast cancer. Methods: MTT, migration/invasion assay, cell cycle analysis, apoptosis assay were performed in MCF-7 and T47D cells estrogen receptor (ER) positive breast cancer cells). Gene expression was investigated by real-time PCR and detection of CAMP in serum was evaluated by ELISA. Co-culture assay of breast cancer cells and macrophages was carried out by using the 0.4µm pore transwell. Immunofluorescence staining was introduced to investigate the cellular expression in macrophages and cancer cells. Results: CAMP was overexpressed in cancer tissues and serum of breast cancer patients. CAMP knockdown led to decreased cell proliferation, inhibited migration/invasion ability, which was associated with G1 phase cell cycle arrest, increased early apoptosis and alteration in epithelial mesenchymal transition (EMT)-related genes. CAMP expression was altered during macrophage M1/M2 polarization and was released predominantly in M2 phenotype. In addition, breast cancer cells co-cultured with macrophages showed upregulated CAMP expression and also increased cancer cell viability. Conclusions: Our data implicated that CAMP confers oncogenic role in breast cancer and it plays important role in the tumor microenvironment between TAMs and breast cancer cells. These findings provide novel therapeutic options for this malignant disease.