Effect of antibacterial peptide hCAP18/LL-37 on ovarian cancer microenvironment and the regulatory mechanism of its expression.
- Author:
Qian LU
1
;
Wenqiang QUAN
1
;
Junlu WU
1
;
Xian ZHANG
1
;
Wei MA
1
;
Li PANG
1
;
Dong LI
2
;
Email: 186LD@163.COM.
Author Information
- Publication Type:Journal Article
- MeSH: Antimicrobial Cationic Peptides; metabolism; pharmacology; Cell Line, Tumor; Coculture Techniques; Collagen; Drug Combinations; Female; Humans; Laminin; Macrophages; metabolism; Neoplasm Invasiveness; Neoplasm Proteins; metabolism; Ovarian Neoplasms; metabolism; pathology; physiopathology; Plasmids; Proteoglycans; RNA, Messenger; metabolism; RNA, Small Interfering; Real-Time Polymerase Chain Reaction; Transfection; Tumor Microenvironment; drug effects; Versicans; metabolism
- From: Chinese Journal of Oncology 2015;37(10):725-730
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of antibacterial peptide hCAP18/LL-37 on ovarian cancer microenvironment and the regulatory mechanism of its expression.
METHODSWe assessed the effect of macrophage-promoted ovarian cancer cells invasion using BioCoat Matrigel invasion chamber. The expressions of hCAP18/LL-37 and versican V1 were determined by real-time PCR and Western blot analysis. SKOV3 cells were transfected with shRNA plasmid to abrogate the expression of versican V1, and then the expression of hCAP18/LL-37 in macrophages and the invasiveness of SKOV3 cells were assayed.
RESULTSThe Matrigel invasion assay showed that after co-culture with macrophages for 4 days, the number of penetrated SKOV3 cells was 112.8±17.1/per high power field, significantly higher than that in the SKOV3 cells cultured alone (8.2±1.9/per high power field) (P<0.05). Addition of hCAP/LL-37 neutralizing antibody into the co-cultured macrophage-SKOV3 cells markedly inhibited the macrophage-promoted SKOV3 cells invasion. The penetrated SKOV3 cells was 22.2±5.6/per high power field, significantly lower than the 100.6±25.2/per high power field in the control macrophage- SKOV3 co-cultured cells (P<0.05). The expressions of hCAP18/LL-37 mRNA and protein in macrophages were remarkably enhanced upon co-culture with SKOV3 cells, but not changed in SKOV3 cells cultured alone. The expression and secretion of versican V1 in the ovarian cancer cells were also significantly increased after co-cultured with macrophages. Knockdown of versican V1 in SKOV3 cells by small interfering RNA significantly reduced the expression of hCAP18/LL-37 mRNA and protein in the macrophages, as well as decreased the invasiveness of SKOV3 cells (P<0.05).
CONCLUSIONSIn the cancer microenvironment, the macrophage-secreted hCAP18/LL-37 promote the invasiveness of ovarian cancer cells, and the hCAP18/LL-37 expression is regulated by versican V1 protein released by ovarian cancer cells.