Recombinant bactericidal permeability increasing protein (rBPI ₂₁) 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, rBPI₂₁ would block surgeryinduced 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 rBPI₂₁ 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 rBPI₂₁ attenuated this increased growth and decreased proliferation, increased apoptosis, decreased micro-vessel density and circulating VEGF. This suggests that rBPI₂₁, has clinical potential in attenuating surgery enhanced tumour growth, especially in patients with a history of cancer undergoing laparotomy.