Modulating the internalization of bacille Calmette-Guérin by cathelicidin in bladder cancer cells.
Choi. Se Young SY; Kim. Soon-Ja SJ; Chi. Byung Hoon BH; Kwon. Jong Kyou JK; Chang. In Ho IH
Key Findings
- Bladder cancer cells increase LL‑37 production after BCG exposure.
- Adding extra LL‑37 lowers how much BCG can enter the cancer cells.
- Blocking LL‑37 with an antibody raises BCG internalization and reduces cancer cell viability.
Practical Outcomes
- For the biohacker community focused on general health and performance, this research has little direct use. It is specific to bladder cancer therapy and does not suggest any actionable protocol for longevity, metabolism, or everyday supplementation.
Summary
The study shows that bladder cancer cells make more of the peptide LL‑37 when they are exposed to the BCG vaccine used in bladder cancer treatment. Higher LL‑37 levels actually block BCG from getting inside the cancer cells, which reduces the vaccine's ability to kill the cells. When LL‑37 is blocked with an antibody, more BCG gets inside and the cancer cells die more.
Abstract
To confirm the role of cathelicidin (LL-37) in the internalization of bacille Calmette-Guérin (BCG) into bladder cancer cells. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction analysis evaluated the changes in protein and messenger ribonucleic acid (RNA) expression with BCG incubation after LL-37 pretreatment in 5637 and T24 human bladder cancer cells. The internalization rate was evaluated by a double immunofluorescence assay, and confocal microscopy confirmed the function of LL-37 in BCG internalization. We also investigated the difference in internalization rates and cell viability between LL-37, anti-LL-37 antibody, and LL-37 plus anti-LL-37 antibody. The levels of LL-37 increased after BCG exposure in bladder cancer cells in dose- and time-dependent manners. Increasing LL-37 levels using recombinant LL-37 protein further dose dependently decreased BCG internalization in both cell lines. The internalization rates of BCG after LL-37 instillation were lower compared with the controls, and the internalization rate of BCG after anti-LL-37 antibody instillation was significantly higher compared with the controls in both cell lines (P <.05). Viability of LL-37 plus BCG group was higher compared with the BCG-alone group. The anti-LL-37 antibody plus BCG group had decreased cell viability compared with the BCG-alone group in both cell lines. Bladder cancer cells produce cathelicidin when infected with BCG and upregulate cathelicidin to defend against BCG by inhibiting its internalization. Blocking the action of cathelicidin may increase the internalization and effectiveness of BCG in reducing bladder cancer cell proliferation.
Study Information
pubmed
2015
2015-02-11T00:00:00.000Z
10.1016/j.urology.2014.12.028
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