Human Monocytes Both Enhance and Inhibit the Growth of Human Pancreatic Cancer in SCID Mice

Abstract

Background: Monocytes/macrophages exhibit antitumour potential, but clinicopathological evidence suggests that they may both inhibit and enhance tumour growth. The purpose of this study was to determine the effect of monocytes on the growth of human pancreatic cancer (HPC-4) in severe combined immunodeficient (SCID) mice. Materials and Methods: Freshly isolated human monocytes or CD14⁺ cells from cocultures with tumour cells were coengrafted, at various ratios, with HPC-4 cells into SCID mice. The tumour size and angiogenesis were determined. Results: At a high ratio of monocytes to cancer cells the enhancement and, at a low ratio, the inhibition of tumour growth was observed. Multiple intratumoral applications of monocytes in large numbers also enhanced tumour growth. Deactivation of monocytes by a short pre-exposure to tumour cells in vitro before engraftment led to increased tumour growth. Monocytes used in large numbers and deactivated monocytes in low doses enhanced tumour-induced angiogenesis. Conclusion: Monocytes may both facilitate and suppress the growth of human tumours in SCID mice and both the number of monocytes, as well as the state of monocyte deactivation are critical for the final outcome of monocyte-tumour interactions.