Antitumor activity of liposomal prednisolone phosphate depends on the presence of functional tumor-associated macrophages in tumor tissue.
Prednisolone phosphate (PLP) encapsulated in long-circulating liposomes (LCLs) (LCL-PLP) exerts antitumor activity through the inhibition of tumor angiogenesis. It is known that tumor-associated macrophages (TAMs) play a crucial role in tumor growth as they are actively involved in promoting and maintaining tumor angiogenesis. To gain more insight into the antiangiogenic mechanisms of LCL-PLP, this study aimed to investigate the role of TAM in the antitumor mode of action of LCL-PLP in B16.F10 melanoma-bearing mice. Our results show that TAMs have a pivotal function in the growth of B16.F10 melanoma through the production of pro-angiogenic/pro-inflammatory factors. One of the major inhibitory actions of LCL-PLP on tumor growth is the reduction of the TAM-mediated production of pro-angiogenic factors, whereas production of anti-angiogenic factors by these cells is hardly affected.
Banciu
Manuela
M
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands. covaciumanu@yahoo.com
Metselaar
Josbert M
JM
Schiffelers
Raymond M
RM
Storm
Gert
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004002:Clodronic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D008081:Liposomes; D004002:Clodronic Acid; C009022:prednisolone phosphate; D011239:Prednisolone