Models of monocytic invasion into glioma cell aggregates

Abstract

Background: In order to investigate why human gliomas are abundantly infiltrated by monocytic cells without signs of antitumor activity, experimental models were established in vitro and in vivo. Materials and Methods: Peripheral human blood monocytes were added to A 772 or U118 glioma cell spheroids and probes analyzed after 72 h by immunohistochemistry. Fluorescence-labelled peritoneal macrophages were administered to syngeneic RG2-gliomabearing Fischer rats by intravenous or intracarotid injection. Results: Spheroids of both cell lines were infiltrated by monocytes, which took on a chronic inflammatory phenotype with co-expression of MRP8 and MAC 3871 MRP14 and positivity to 25F9, but not to 27E10. After both intra-arterial and intravenous injection, labelled monocytes accumulated within the tumor parenchyma of the rat gliomas, while the surrounding brain was only sparsely infiltrated. Conclusion: The experimental models described here allow for further investigation of the interactions between monocytes and glioma cells, both in vitro and in vivo. Moreover, monocytes that infiltrate from the peripheral blood into brain tumors may serve as carriers for targeted therapies.