Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer.

Weber G, Chamorro CI, Granath F, Liljegren A, Zreika S, Saidak Z, Sandstedt B, Rotstein S, Mentaverri R, Sánchez F, Pivarcsi A, Ståhle M

Breast cancer research : BCR30 Jan 2009Cited by 72 (Europe PMC)

PMID19183447PMCIDPMC2687709DOI10.1186/bcr2221PepBankPUB-19183447

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Summary

IntroductionHuman cathelicidin antimicrobial protein, hCAP18, and its C-terminal peptide LL-37 is a multifunctional protein. In addition to being important in antimicrobial defense, it induces chemotaxis, stimulates angiogenesis and promotes tissue repair. We previously showed that human breast cancer cells express high amounts of hCAP18, and hypothesised that hCAP18/LL-37 may be involved in tumour progression.MethodshCAP18 mRNA was quantified in 109 primary breast cancers and compared with clinical findings and ERBB2 mRNA expression. Effects of exogenous LL-37 and transgenic overexpression of hCAP18 on ErbB2 signalling were investigated by immunoblotting using extracts from breast cancer cell lines ZR75-1 and derivatives of MCF7. We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.ResultsThe expression of hCAP18 correlated closely with that of ERBB2 and with the presence of lymph node metastases in oestrogen receptor-positive tumours. hCAP18/LL-37 amplified Heregulin-induced mitogen-activated protein kinase (MAPK) signalling through ErbB2, identifying a functional association between hCAP18/LL-37 and ErbB2 in breast cancer. Treatment with LL-37 peptide significantly stimulated the migration of breast cancer cells and their colonies acquired a dispersed morphology indicative of increased metastatic potential. A truncated version of LL-37 competitively inhibited LL-37 induced MAPK phosphorylation and significantly reduced the number of altered cancer cell colonies induced by LL-37 as well as suppressed their migration. Transgenic overexpression of hCAP18 in a low malignant breast cancer cell line promoted the development of metastases in SCID mice, and analysis of hCAP18 transgenic tumours showed enhanced activation of MAPK signalling.ConclusionsOur results provide evidence that hCAP18/LL-37 contributes to breast cancer metastasis.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

3 results from studies that gave the peptide. No result from this study comes from people.

01LabIn vitro (cells)Mechanism
In breast cancer cell lines, hCAP18/LL‑37 amplified Heregulin-induced MAPK signalling through ErbB2.
In plain wordsIn cells, hCAP18/LL‑37 boosted a growth signal in breast cancer cells.
Peptide
LL-37
Outcome
IncreaseHeregulin-induced MAPK signalling through ErbB2
Study
humann: not reported in source
Breast cancer cell lines ZR75-1 and MCF7 derivatives
Outcome group
Receptor activity and mechanism · Cancer
Studied dose
Dose not stated
Source sentences
Summary
hCAP18/LL-37 amplified Heregulin-induced mitogen-activated protein kinase (MAPK) signalling through ErbB2, identifying a functional association between hCAP18/LL-37 and ErbB2 in breast cancer.
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of exogenous LL-37 and transgenic overexpression of hCAP18 on ErbB2 signalling were investigated by immunoblotting using extracts from breast cancer cell lines ZR75-1 and derivatives of MCF7.
Show in the study text Report a problemFND-1918344703
02LabIn vitro (cells)Activity measurement
In breast cancer cells, treatment with LL‑37 peptide significantly stimulated cell migration.
In plain wordsIn cells, LL‑37 made breast cancer cells move more.
Peptide
LL-37
Outcome
IncreaseBreast cancer cell migration
Study
humann: not reported in source
Breast cancer cell lines
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated
Source sentences
Summary
Treatment with LL-37 peptide significantly stimulated the migration of breast cancer cells
1 context sentence(design, population, supporting numbers)
Summary · context
We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.
Show in the study text Report a problemFND-1918344704
03LabIn vitro (cells)Activity measurement
In breast cancer cells grown in soft agar, LL‑37 treatment gave colonies a dispersed morphology indicative of increased metastatic potential.
In plain wordsIn cells, LL‑37 changed the shape of breast cancer cell colonies in a way that suggests a higher chance of spread.
Peptide
LL-37
Outcome
Not applicableColony morphology in soft agar
Study
humann: not reported in source
Breast cancer cells grown in soft agar
Outcome group
Tumor growth · Cancer
Studied dose
Dose not stated
Source sentences
Summary
their colonies acquired a dispersed morphology indicative of increased metastatic potential.
1 context sentence(design, population, supporting numbers)
Summary · context
We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.
Show in the study text Report a problemFND-1918344705

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

04HumanEndogenous levelObservational studyOther
In 109 primary breast cancers, hCAP18 mRNA expression correlated closely with ERBB2 mRNA expression.
In plain wordsIn breast tumours, the body's own hCAP18 levels rose together with ERBB2 levels.
Peptide
LL-37
Outcome
IncreasehCAP18 mRNA correlation with ERBB2 mRNA in primary breast cancers
Study
n = 109
Outcome group
Tumor growth · Cancer
Source sentences
Summary
The expression of hCAP18 correlated closely with that of ERBB2
1 context sentence(design, population, supporting numbers)
Summary · context
hCAP18 mRNA was quantified in 109 primary breast cancers and compared with clinical findings and ERBB2 mRNA expression.
This result measures the body's own LL-37. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-1918344701
05HumanEndogenous levelObservational studyOther
In oestrogen receptor-positive primary breast cancers, hCAP18 mRNA expression correlated with the presence of lymph node metastases.
In plain wordsIn breast tumours that respond to oestrogen, the body's own hCAP18 levels were linked to cancer spread to lymph nodes.
Peptide
LL-37
Outcome
IncreasehCAP18 mRNA and lymph node metastases in oestrogen receptor-positive tumours
Study
n: not reported in source
Outcome group
Tumor growth · Cancer
Source sentences
Summary
The expression of hCAP18 correlated closely with that of ERBB2 and with the presence of lymph node metastases in oestrogen receptor-positive tumours
1 context sentence(design, population, supporting numbers)
Summary · context
hCAP18 mRNA was quantified in 109 primary breast cancers and compared with clinical findings and ERBB2 mRNA expression.
This result measures the body's own LL-37. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-1918344702

Studies that did not test the peptide alone5

In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking LL-37.

06AnimalNot a test of LL-37 aloneAnimal study (in vivo)Efficacy outcome
In SCID mice, transgenic overexpression of hCAP18 in a low malignant breast cancer cell line promoted the development of metastases.
In plain wordsIn mice, breast cancer cells made to produce extra hCAP18 spread more.
Peptide
LL-37
Outcome
IncreaseMetastasis development with hCAP18 overexpression
Study
mousen: not reported in source
SCID mice with low malignant breast cancer cells overexpressing hCAP18
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Transgenic overexpression of hCAP18 in a low malignant breast cancer cell line promoted the development of metastases in SCID mice
1 context sentence(design, population, supporting numbers)
Summary · context
We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.
In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LL-37.
Show in the study text Report a problemFND-1918344709
07AnimalNot a test of LL-37 aloneAnimal study (in vivo)Mechanism
In SCID mice, hCAP18 transgenic tumours showed enhanced activation of MAPK signalling.
In plain wordsIn mice, tumours made to produce extra hCAP18 showed stronger growth signalling.
Peptide
LL-37
Outcome
IncreaseMAPK activation in hCAP18 transgenic tumours
Study
mousen: not reported in source
SCID mice with hCAP18 transgenic tumours
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
analysis of hCAP18 transgenic tumours showed enhanced activation of MAPK signalling.
1 context sentence(design, population, supporting numbers)
Summary · context
We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.
In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LL-37.
Show in the study text Report a problemFND-1918344710
08LabNot a test of LL-37 aloneIn vitro (cells)Mechanism
In breast cancer cells, a truncated version of LL‑37 competitively inhibited LL‑37-induced MAPK phosphorylation.
In plain wordsIn cells, a shortened form of LL‑37 blocked a growth signal that LL‑37 switched on.
Peptide
LL-37
Outcome
DecreaseLL-37-induced MAPK phosphorylation with truncated LL-37
Study
humann: not reported in source
Breast cancer cell lines
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
A truncated version of LL-37 competitively inhibited LL-37 induced MAPK phosphorylation
1 context sentence(design, population, supporting numbers)
Summary · context
Effects of exogenous LL-37 and transgenic overexpression of hCAP18 on ErbB2 signalling were investigated by immunoblotting using extracts from breast cancer cell lines ZR75-1 and derivatives of MCF7.
In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LL-37.
Show in the study text Report a problemFND-1918344706
09LabNot a test of LL-37 aloneIn vitro (cells)Activity measurement
In breast cancer cells in soft agar, a truncated version of LL‑37 significantly reduced the number of altered colonies induced by LL‑37.
In plain wordsIn cells, a shortened form of LL‑37 reduced the odd colonies that LL‑37 caused.
Peptide
LL-37
Outcome
DecreaseLL-37-induced altered colonies with truncated LL-37
Study
humann: not reported in source
Breast cancer cells grown in soft agar
Outcome group
Tumor growth · Cancer
Source sentences
Summary
significantly reduced the number of altered cancer cell colonies induced by LL-37 as well as suppressed their migration.
1 context sentence(design, population, supporting numbers)
Summary · context
We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.
In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LL-37.
Show in the study text Report a problemFND-1918344707
10LabNot a test of LL-37 aloneIn vitro (cells)Activity measurement
In breast cancer cells, a truncated version of LL‑37 suppressed cell migration.
In plain wordsIn cells, a shortened form of LL‑37 slowed the movement of breast cancer cells.
Peptide
LL-37
Outcome
DecreaseCancer cell migration with truncated LL-37
Study
humann: not reported in source
Breast cancer cell lines
Outcome group
Tumor growth · Cancer
Source sentences
Summary
as well as suppressed their migration.
1 context sentence(design, population, supporting numbers)
Summary · context
We further analysed the impact of hCAP18/LL-37 on the morphology of breast cancer cells grown in soft agar, on cell migration and on tumour development in severe combined immunodeficiency (SCID) mice.
In this study, LL-37 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LL-37.
Show in the study text Report a problemFND-1918344708

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 2
9 Oct 2026, 03:03 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 02:58 UTC
First added · source update from Europe PMC

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