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.
Keywords: Placental growth factor (PlGF); antiangiogenic therapy; renal cell carcinoma; sunitinib resistance.
Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.