Hideharu Bessho1, Bernice Wong2, Dan Huang3, Ee Yan Siew2, Dachuan Huang2, Jing Tan2, Choon Kiat Ong2, Soo Yong Tan4, Kazumasa Matsumoto5, Masatsugu Iwamura5, Bin Tean Teh6. 1. Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan hideji56@gmail.com. 2. Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore. 3. Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI, U.S.A. 4. Department of Pathology, Singapore General Hospital, Singapore, Singapore. 5. Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan. 6. Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Abstract
BACKGROUND/AIM: Placental growth factor (PlGF) is up-regulated in major malignant diseases or following antiangiogenic therapy, although it is present in low levels under normal physiological conditions. TB403, a monoclonal antibody against PlGF, was investigated in clear cell renal cell carcinoma (ccRCC) xenografts since it has been proposed as a potential target in oncology. MATERIALS AND METHODS: Human ccRCCs were implanted in athymic nude mice to evaluate the efficacy of TB403 and to excise xenograft tumors for molecular experiments. RESULTS: TB403 did not significantly inhibit tumor growth in treatment-naïve or sunitinib-resistant ccRCC xenografts. Gene expression profiling resulted in over-expression of the C1orf38 gene, which induced immunoreactivity in macrophages. Angiogenesis PCR arrays showed that VEGFR-1 was not expressed in ccRCC xenografts. CONCLUSION: PlGF blockade did not have a broad antiangiogenic efficacy; however, it might be effective on-target in VEGFR1-expressing tumors. The inhibition of VEGF pathway may induce the activity of tumor-associated-macrophages for angiogenesis escape. Copyright
BACKGROUND/AIM: Placental growth factor (PlGF) is up-regulated in major malignant diseases or following antiangiogenic therapy, although it is present in low levels under normal physiological conditions. TB403, a monoclonal antibody against PlGF, was investigated in clear cell renal cell carcinoma (ccRCC) xenografts since it has been proposed as a potential target in oncology. MATERIALS AND METHODS:Human ccRCCs were implanted in athymic nude mice to evaluate the efficacy of TB403 and to excise xenograft tumors for molecular experiments. RESULTS:TB403 did not significantly inhibit tumor growth in treatment-naïve or sunitinib-resistant ccRCC xenografts. Gene expression profiling resulted in over-expression of the C1orf38 gene, which induced immunoreactivity in macrophages. Angiogenesis PCR arrays showed that VEGFR-1 was not expressed in ccRCC xenografts. CONCLUSION:PlGF blockade did not have a broad antiangiogenic efficacy; however, it might be effective on-target in VEGFR1-expressing tumors. The inhibition of VEGF pathway may induce the activity of tumor-associated-macrophages for angiogenesis escape. Copyright