Journal
MOLECULAR CANCER RESEARCH
Volume 7, Issue 12, Pages 1920-1927Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-09-0041
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Funding
- Korea Science and Engineering Foundation (KOSEF) [R01-2007-000-11236-0]
- Innovative Research Institute for Cell Therapy [A062260]
- KOSEF through the Infection Signaling Network Research [R13-2007-020-01000-0]
- National Research Foundation of Korea [R01-2007-000-11236-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Chemotherapy is often hindered by abnormal tumor vascularity, which causes impaired delivery of drugs into the tumor. Angiopoietin-1 has potent roles in angiogenesis and vessel maturation. We report here that an angiopoietin-1 variant, COMP-Ang1, promotes vascular remodeling and pericyte coverage and thereby promotes the efficient delivery of a chemotherapeutic drug into tumors of murine Lewis lung carcinoma. The combination of COMP-Ang1 with the cytotoxic drug 5-fluorouracil potentiated the effect of 5-fluorouracil on tumor growth without increasing animal toxicity. Moreover, COMP-Ang1 increased perfusion into the tumor. Although COMP-Ang1 increased the functional vasculature in the tumor, COMP-Ang1 alone did not promote tumor growth, possibly due to its promotion of increased pericyte coverage. This study suggests that COMP-Ang1 may improve the microcirculation within a tumor by increasing functional vasculature and tissue perfusion and that the combination of chemotherapy together with COMP-Ang1 might be an advantageous therapeutic approach. (Mol Cancer Res 2009;7(12):1920-7)
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