Discrepancies between antiangiogenic and antitumor effects of recombinant human endostatin.
It has been widely accepted that antiangiogenesis therapy could deprive tumor cells of nutrients and oxygen and suppress tumor growth. However, in the present study, Lewis lung carcinomas and A549 adenocarcinomas established in male C57BL/6 and BALB/c nude mice, respectively, were treated with recombinant human endostatin (rh-endostatin). Earlier studies document discrepancies in the antiangiogenic and antitumor outcomes of rh-endostatin treatment, at doses equivalent to clinical usage. Although there was no significant regression of tumor growth, tumor vasculature was widely disrupted within the first few days of treatment with rh-endostatin, as indicated by reduced blood perfusion (visualized by dynamic-contrast-enhanced magnetic resonance imaging) and reduced microvascular density. Interestingly, when rh-endostatin treatment was discontinued, there was an elevation in the diffusion of oxygen and tetramethylrhodamine isothiocyanate-dextran in both tumor classes, which was detected by hypoxyprobe (pimonidazole) and fluorescence microscopy. We conclude that the paradoxic outcomes in the antiangiogenic and antitumor properties of rh-endostatin might derive from the tumors' tolerance to antiangiogenesis inhibitors. Additionally, rh-endostatin might have the ability to transiently normalize tumor vasculature.
Huang
Guichun
G
Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, People's Republic of China.
Chen
Longbang
L
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology; D043169:Endostatins / Q000737:chemistry*; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008833:Microcirculation; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000737:chemistry*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D043169:Endostatins; D011994:Recombinant Proteins