Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion.
Coffelt. Seth B SB; Waterman. Ruth S RS; Florez. Luisa L; Höner zu Bentrup. Kerstin K; Zwezdaryk. Kevin J KJ; Tomchuck. Suzanne L SL; LaMarca. Heather L HL; Danka. Elizabeth S ES; Morris. Cindy A CA; Scandurro. Aline B AB
Key Findings
- Ovarian cancer tissues have significantly higher levels of LL‑37 compared to normal ovaries
- Adding LL‑37 to ovarian cancer cells in the lab boosted their proliferation, movement, invasion, and matrix‑metalloproteinase production
- Higher LL‑37 levels in tumors were linked to more immune‑cell infiltration and higher microvessel density, indicating a role in tumor growth and angiogenesis
Practical Outcomes
- For biohackers, this suggests that increasing LL‑37 (e.g., via supplements or interventions that raise its levels) could potentially raise cancer risk, especially in tissues prone to tumor development. There’s no actionable benefit for longevity or performance, and caution is advised against trying to boost this peptide without medical supervision.
Summary
The study found that the antimicrobial peptide LL‑37, normally part of our immune system, is found in much higher amounts in ovarian tumors and actually makes cancer cells grow and spread faster, while also promoting blood vessel formation and attracting immune cells to the tumor.
Abstract
The role of the pro-inflammatory peptide, LL-37, and its pro-form, human cationic antimicrobial protein 18 (hCAP-18), in cancer development and progression is poorly understood. In damaged and inflamed tissue, LL-37 functions as a chemoattractant, mitogen and pro-angiogenic factor suggesting that the peptide may potentiate tumor progression. The aim of this study was to characterize the distribution of hCAP-18/LL-37 in normal and cancerous ovarian tissue and to examine the effects of LL-37 on ovarian cancer cells. Expression of hCAP-18/LL-37 was localized to immune and granulosa cells of normal ovarian tissue. By contrast, ovarian tumors displayed significantly higher levels of hCAP-18/LL-37 where expression was observed in tumor and stromal cells. Protein expression was statistically compared to the degree of immune cell infiltration and microvessel density in epithelial-derived ovarian tumors and a significant correlation was observed for both. It was demonstrated that ovarian tumor tissue lysates and ovarian cancer cell lines express hCAP-18/LL-37. Treatment of ovarian cancer cell lines with recombinant LL-37 stimulated proliferation, chemotaxis, invasion and matrix metalloproteinase expression. These data demonstrate for the first time that hCAP-18/LL-37 is significantly overexpressed in ovarian tumors and suggest LL-37 may contribute to ovarian tumorigenesis through direct stimulation of tumor cells, initiation of angiogenesis and recruitment of immune cells. These data provide further evidence of the existing relationship between pro-inflammatory molecules and ovarian cancer progression.
Study Information
pubmed
2008
2008-03-01T00:00:00.000Z
10.1002/ijc.23186
112
46