Neutralization of CCL2 inhibits tumor angiogenesis and pancreatic tumor growth

A69 CCL2 (also known as monocyte chemoattractant protein-1 or MCP-1) is a potent chemoattractant of monocytes and has been shown to play a role in promoting tumor angiogenesis and proliferation. CCL2 expressed by the tumor may recruit tumor-associated macrophages (TAMs), which produce pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF), TNFα, IL-6 and IL-8. In some cancer types, CCL2 expression in the primary tumor has been correlated with macrophage infiltration and blood vessel density, and these in turn are correlated with disease stage and prognosis. If CCL2 is a key factor in these activities, we hypothesized that neutralization of CCL2 could inhibit tumor growth and provide clinical benefit to cancer patients.
 The purpose of these studies was to assess the role of CCL2 and the efficacy of CCL2 blockade in pancreatic tumor angiogenesis and tumor growth models. The studies used the PANC-1 and BxPC3 pancreatic tumor lines, which express different levels of CCL2 in vitro (~90 ng and 6 cells/day, respectively). In addition, these cell lines express CCR2, the CCL2 receptor, indicating a mechanism by which the tumor cells could respond to the presence of CCL2 in the tumor microenvironment.
 Neutralizing antibodies to human CCL2 (CNTO 888; does not neutralize mouse MCP-1) and mouse MCP-1 (anti-MCP-1; does not neutralize human CCL2) were used to determine the impact of blocking CCL2 and/or MCP-1 in tumor-mediated angiogenesis and tumor growth. Both CNTO 888 and anti-MCP-1 showed dose-dependent inhibition of PANC-1-induced angiogenesis in the Matrigel angiogenesis model (p