Recombinant bactericidal permeability increasing protein (rBPI21) inhibits surgery-induced tumour growth in a murine model of metastatic disease.
BACKGROUND
Endotoxin (LPS), a cell wall constituent of gram-negative bacteria, is a potent inflammatory stimulus. We demonstrated that laparotomy increases primary tumour growth and experimental lung metastases, implicating endotoxin as a causative factor. We hypothesised that the anti-endotoxin agent, rBPI(21) would block surgery-induced tumour growth.


METHODS
Mammary adenocarcinoma cells were injected into female BALB/c mice to establish lung metastases. Mice were randomised into three groups receiving anaesthesia, laparotomy or laparotomy and rBPI(21) treatment on day 14. Animals were killed on day 19, lungs harvested and blood obtained. Number and size of lung metastases were recorded. Apoptosis, mitosis and microvessel density within metastases were assessed and VEGF measured.


CONCLUSIONS
Laparotomy increased metastatic growth, decreased tumour cell apoptosis, increased tumour cell proliferation, increased microvessel density and circulating VEGF. LPS blockade by rBPI(21) attenuated this increased growth and decreased proliferation, increased apoptosis, decreased micro-vessel density and circulating VEGF. This suggests that rBPI(21), has clinical potential in attenuating surgery enhanced tumour growth, especially in patients with a history of cancer undergoing laparotomy.
Symptomatic Breast Health Unit, Mater Misericordiae University Hospital, 38 Eccles Street, Dublin 7, Ireland. gerodonoghue@rcsi.ie
G T
GT
O'Donoghue
G P
GP
Pidgeon
J H
JH
Harmey
R
R
Dedrick
H P
HP
Redmond
D J
DJ
Bouchier-Hayes
D000230:Adenocarcinoma / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000276:immunology; D001798:Blood Proteins / Q000276:immunology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology; D007813:Laparotomy / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000473:pathology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000473:pathology; D011897:Random Allocation; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use*; D000267:Tissue Adhesions / Q000150:complications; D042461:Vascular Endothelial Growth Factor A
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D001798:Blood Proteins; D004731:Endotoxins; D008565:Membrane Proteins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C021623:bactericidal permeability increasing protein