The Role of Cathelicidin LL-37 in Cancer Development

Piktel, Ewelina; Niemirowicz, Katarzyna; Wnorowska, Urszula; Wątek, Marzena; Wollny, Tomasz; Głuszek, Katarzyna; Góźdż, Stanisław; Levental, Ilya; Bucki, Robert

doi:10.1007/s00005-015-0359-5

Cited by 89 publications

(110 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cathelicidins are antimicrobial peptides produced by mammals in response to various pathogenic microbes [1][2][3][4][5]. Human cathelicidin antimicrobial peptide (CAMP, hCAP-18) is the only member of the cathelicidin protein family in humans [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…Human cathelicidin antimicrobial peptide (CAMP, hCAP-18) is the only member of the cathelicidin protein family in humans [1][2][3][4][5]. hCAP-18 (18kDa) is processed by proteolytic cleavage to bioactive cathelicidin LL-37 (37 amino acid residues with diLeucine at the N-terminus) by exposure to specific serine proteases like proteinase 3, kallikrein 5 and kallikrein 7 [1].…”

Section: Introductionmentioning

confidence: 99%

“…hCAP-18 (18kDa) is processed by proteolytic cleavage to bioactive cathelicidin LL-37 (37 amino acid residues with diLeucine at the N-terminus) by exposure to specific serine proteases like proteinase 3, kallikrein 5 and kallikrein 7 [1]. hCAP-18 is widely expressed in various epithelial cells Ovarian cancer LL-37 expression levels significantly increase in ovarian cancer tissues compared to the normal ovary tissues suggesting it might be a potential biomarker of ovarian cancer [2,35]. In ovarian cancer cells, recombinant LL-37 induces cell proliferation, cell invasion, chemotaxis, and matrix metalloproteinase (MMP) expression [35].…”

Section: Introductionmentioning

confidence: 99%

“…Lung cancer hCAP-18/LL-37 is expressed at elevated levels in human lung cancer cells at both the mRNA and protein levels [2,42,46,47]. Lung cancer cell lines that stably overexpress the hCAP-18 peptide also grow faster [46].…”

Section: Introductionmentioning

confidence: 99%

“…LL-37 activates the EGFR through MMP-mediated cleavage of membrane-anchored EGFR-ligands (Fig. 2B) [2,48]. On the other hand, IL-32 expression is distinctly altered in lung cancer cells and closely associated with increased lung cancer invasiveness, metastasis and poor prognosis [48,49].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Chen

Zou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

LL-37, the C-terminal peptide of human cathelicidin antimicrobial peptide (CAMP, hCAP18), reportedly increases resistance to microbial invasion and exerts important physiological functions in chemotaxis, promotion of wound closure, and angiogenesis. Accumulating evidence indicates that LL-37 also plays a significant role in human cancer. LL-37 induces tumorigenic effects in cancers of the ovary, lung, breast, prostate, pancreas, as well as in malignant melanoma and skin squamous cell carcinoma. In contrast, LL-37 displays an anti-cancer effect in colon cancer, gastric cancer, hematologic malignancy and oral squamous cell carcinoma. Mechanistically, LL-37-induced activation of membrane receptors and subsequent signaling pathways lead to alteration of cellular functions. Different membrane receptors on various cancer cells appear to be responsible for the tissue-specific effects of LL-37. Meanwhile, the findings that vitamin D-dependent induction of cathelicidin in human macrophages activates the anti-cancer activity of tumor-associated macrophages (TAMs) and enhances antibody-dependent cellular cytotoxicity (ADCC) support critical roles of vitamin D-dependent induction of cathelicidin in cancer progression. This review describes novel advances involving the roles and mechanisms of human cathelicidin LL-37 in cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Chen

Zou

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

Colonic epithelial cathelicidin (LL‐37) expression intensity is associated with progression of colorectal cancer and presence of CD8⁺ T cell infiltrate

Porter

Murray

Alnabulsi

et al. 2021

The Journal of Pathology CR

View full text Add to dashboard Cite

Colorectal cancer (CRC) remains a leading cause of cancer mortality. Here, we define the colonic epithelial expression of cathelicidin (LL‐37) in CRC. Cathelicidin exerts pleotropic effects including anti‐microbial and immunoregulatory functions. Genetic knockout of cathelicidin led to increased size and number of colorectal tumours in the azoxymethane‐induced murine model of CRC. We aimed to translate this to human disease. The expression of LL‐37 in a large (n = 650) fully characterised cohort of treatment‐naïve primary human colorectal tumours and 50 matched normal mucosa samples with associated clinical and pathological data (patient age, gender, tumour site, tumour stage [UICC], presence or absence of extra‐mural vascular invasion, tumour differentiation, mismatch repair protein status, and survival to 18 years) was assessed by immunohistochemistry. The biological consequences of LL‐37 expression on the epithelial barrier and immune cell phenotype were assessed using targeted quantitative PCR gene expression of epithelial permeability (CLDN2, CLDN4, OCLN, CDH1, and TJP1) and cytokine (IL‐1β, IL‐18, IL‐33, IL‐10, IL‐22, and IL‐27) genes in a human colon organoid model, and CD3+, CD4+, and CD8+ lymphocyte phenotyping by immunohistochemistry, respectively. Our data reveal that loss of cathelicidin is associated with human CRC progression, with a switch in expression intensity an early feature of CRC. LL‐37 expression intensity is associated with CD8+ T cell infiltrate, influenced by tumour characteristics including mismatch repair protein status. There was no effect on epithelial barrier gene expression. These data offer novel insights into the contribution of LL‐37 to the pathogenesis of CRC and as a therapeutic molecule.

show abstract

Why to target G‐quadruplexes using peptides: Next‐generation G4‐interacting ligands

Sharma

Kundu

Kaur

et al. 2023

Journal of Peptide Science

View full text Add to dashboard Cite

Guanine‐rich oligonucleotides existing in both DNA and RNA are able to fold into four‐stranded DNA secondary structures via Hoogsteen type hydrogen‐bonding, where four guanines self‐assemble into a square planar arrangement, which, when stacked upon each other, results in the formation of higher‐order structures called G‐quadruplexes. Their distribution is not random; they are more frequently present at telomeres, proto‐oncogenic promoters, introns, 5′‐ and 3′‐untranslated regions, stem cell markers, ribosome binding sites and so forth and are associated with various biological functions, all of which play a pivotal role in various incurable diseases like cancer and cellular ageing. Several studies have suggested that G‐quadruplexes could not regulate biological processes by themselves; instead, various proteins take part in this regulation and can be important therapeutic targets. There are certain limitations in using whole G4‐protein for therapeutics purpose because of its high manufacturing cost, laborious structure prediction, dynamic nature, unavailability for oral administration due to its degradation in the gut and inefficient penetration to reach the target site because of the large size. Hence, biologically active peptides can be the potential candidates for therapeutic intervention instead of the whole G4‐protein complex. In this review, we aimed to clarify the biological roles of G4s, how we can identify them throughout the genome via bioinformatics, the proteins interacting with G4s and how G4‐interacting peptide molecules may be the potential next‐generation ligands for targeting the G4 motifs located in biologically important regions.

show abstract

The Role of Cathelicidin LL-37 in Cancer Development

Cited by 89 publications

References 107 publications

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Colonic epithelial cathelicidin (LL‐37) expression intensity is associated with progression of colorectal cancer and presence of CD8⁺ T cell infiltrate

Why to target G‐quadruplexes using peptides: Next‐generation G4‐interacting ligands

Contact Info

Product

Resources

About

The Role of Cathelicidin LL-37 in Cancer Development

Cited by 89 publications

References 107 publications

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Colonic epithelial cathelicidin (LL‐37) expression intensity is associated with progression of colorectal cancer and presence of CD8+ T cell infiltrate

Why to target G‐quadruplexes using peptides: Next‐generation G4‐interacting ligands

Contact Info

Product

Resources

About

Colonic epithelial cathelicidin (LL‐37) expression intensity is associated with progression of colorectal cancer and presence of CD8⁺ T cell infiltrate