Tumor-associated macrophages and angiogenesis

Abstract

Neovascularization, the growth and formation of capillary blood vessels, is an essential component of solid tumor growth. Macrophages have been found to represent a significant component of leukocyte infiltrates associated with tumor. It is apparent that macrophages play a key role in tumor angiogenesis, however that role remains controversial. To investigate the function of macrophages in tumor angiogenesis, we compared the number of blood vessels between control and treatment group of mice. The treatment group was injected with E11 (antibody to human monocyte chemoattractant protein-1 (MCP-1)) in order to block the monocyte recruitment into experimentally implanted tumors, while the other group was injected with controI IgG. Three different kinds of human tumors were inoculated bilaterally into the hind legs of nude mice. Mice were sacrificed at intervals of 4 days, 8 days and 28 days after the initial tumor cell inoculation. All resultant tissue sections were immunostained with MECA 32 (a rat monoclonal antibody)which is known to react with mouse endothelial cells. Positively immunostained blood vessels were then quantified. In the tumors examined, there was no statistically significant difference between the two groups. Inhibition of monocyte recruitment by passive immunization with antibody E11 did not affect tumor-associated angiogenesis, suggesting that there are other important angiogenic mechanisms in some human tumors.