Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells.
Gambade. Audrey A; Zreika. Sami S; Guéguinou. Maxime M; Chourpa. Igor I; Fromont. Gaëlle G; Bouchet. Ana Maria AM; Burlaud-Gaillard. Julien J; Potier-Cartereau. Marie M; Roger. Sébastien S; Aucagne. Vincent V; Chevalier. Stéphan S; Vandier. Christophe C; Goupille. Caroline C; Weber. Günther G
Key Findings
- LL‑37 activates the TRPV2 calcium channel and the BKCa potassium channel, leading to increased calcium entry and cell migration in cancer lines.
- The D‑enantiomer of LL‑37 works just like the natural L‑form, suggesting the peptide acts by altering membrane physical properties rather than binding a specific receptor.
- LL‑37 and TRPV2 expression are positively correlated in human breast tumor samples.
Practical Outcomes
- For biohackers considering LL‑37 supplementation for immune support, this research flags a potential risk: LL‑37 may promote cancer cell migration and metastasis. Until safety is clarified, it’s prudent to avoid LL‑37 use, especially for individuals with a history or risk of cancer. No dosing guidance or beneficial protocol emerges from this study.
Summary
The study shows that the antimicrobial peptide LL‑37 can make cancer cells move faster by opening calcium and potassium channels in the cell membrane. Both the natural (L) and mirror‑image (D) forms do this, meaning the effect is likely due to changes in the membrane itself, not a specific receptor. Higher levels of LL‑37 and the TRPV2 channel were found together in breast tumors.
Abstract
Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects.
Study Information
pubmed
2016
2016-04-26T00:00:00.000Z
10.18632/oncotarget.8122
44
55