[Mechanisms of antimicrobial peptide LL-37 in macrophage-promoted ovarian cancer cell proliferation].
Li. Dong D; Wang. Xuan X; Dai. Yan Y; Yang. Fan F; Wan. Hai-ying HY
Key Findings
- Macrophages co‑cultured with ovarian cancer cells produce more LL‑37 over time.
- Higher LL‑37 levels lead to increased proliferation of three ovarian cancer cell lines (SKOV3, 3AO, HO‑8910).
- Neutralizing LL‑37 with a specific antibody significantly reduces the cancer‑cell growth caused by macrophages.
Practical Outcomes
- For biohackers and self‑experimenters, the data suggest that boosting LL‑37 (e.g., through supplements or gene‑editing) could carry a cancer‑promotion risk, at least for ovarian tissue. It’s a reminder to be cautious with interventions that raise LL‑37 levels and to monitor any immune‑modulating strategies for unintended tumor‑supporting effects.
Summary
The study shows that the antimicrobial peptide LL-37, when released by immune cells called macrophages, can make ovarian cancer cells grow faster. Adding an antibody that blocks LL-37 stopped this extra growth, indicating LL-37 is a key driver in this lab model.
Abstract
The aim of this study was to investigate the role of macrophages in promotion of ovarian tumor cell proliferation mediated by over-expression of antimicrobial peptide LL-37. To co-culture ovarian tumor cells SKOV3, 3AO and HO-8910 with macrophages. The Transwell(®) inserts system was used in the co-culture model. The effect of macrophages promoted ovarian tumor cell proliferation was assessed by BrdU-ELISA and cell number counting. Expressions of mRNA and protein of LL-37 in the macrophages and SKOV3 cells were determined by RT-PCR and Western blot analysis. To observe that LL-37 is responsible for macrophage-promoted ovarian tumor cells growth, LL-37 neutralizing antibody was added to abrogate the LL-37 activation. The cell number assay showed that after 4 days coincubation with macrophages in the proportion of 1:0.5, the number of SKOV3 cells increased from (6.0 ± 0.5)×10(4) to (11.8 ± 1.3)×10(4), showing a significant difference (P < 0.05). It also showed that the growth of the SKOV3 cells was dependent on the macrophage number (P < 0.05). The number variability of 3AO and HO-8910 cells was as the same as SKOV3 cells upon co-culture with macrophages. As determined by BrdU-ELISA, the resulted proliferation of ovarian tumor cells was similar to the result of cell number counting. RT-PCR and Western blot results showed that the expression of LL-37 mRNA and protein in the macrophages was remarkably enhanced in a time dependent manner upon coincubation with SKOV3 cells, but did not work in SKOV3 cells. BrdU-ELISA assay exhibited that treatment of cells with LL-37 significantly stimulated HO-8910 and 3AO cell proliferation. Addition of LL-37 neutralizing antibody markedly inhibited macrophage-promoted ovarian tumor cell (SKOV3, 3AO and HO-8910 cells) proliferation. The OD values of these three cells were decreased from 2.95 ± 0.11 to 1.45 ± 0.04, from 3.39 ± 0.36 to 1.32 ± 0.09 and from 3.93 ± 0.17 to 1.68 ± 0.23, respectively (P < 0.05). Over-expression and release of LL-37 from macrophages is responsible for proliferation of ovarian tumor cells in co-culture condition. The data presented indicate that LL-37 may be critical for macrophage-induced tumor progression.
Study Information
pubmed
2013