التفاصيل البيبلوغرافية
| العنوان: |
Suppressing neutrophil-dependent angiogenesis abrogates resistance to anti-VEGF antibody in a genetic model of colorectal cancer. |
| المؤلفون: |
Yoshiro Itatani, Takamasa Yamamoto, Cuiling Zhong, Molinolo, Alfredo A., Ruppel, Jane, Hegd, Priti, Taketo, M. Mark, Ferraraa, Napoleone |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 9/1/2020, Vol. 117 Issue 35, p1-11, 11p |
| مصطلحات موضوعية: |
COLORECTAL cancer, GENETIC models, NEOVASCULARIZATION, LIVER metastasis, CANCER invasiveness |
| مستخلص: |
We tested cis-ApcΔ716/Smad4+/- and cis-ApcΔ716/Smad4+/- KrasG12D mice, which recapitulate key genetic abnormalities accumulating during colorectal cancer (CRC) tumorigenesis in humans, for responsiveness to anti-VEGF therapy. We found that even tumors in cis-ApcΔ716/Smad4+/- KrasG12D mice, although highly aggressive, were suppressed by anti-VEGF treatment. We tested the hypothesis that inflammation, a major risk factor and trigger for CRC, may affect responsiveness to anti-VEGF. Chemically induced colitis (CIC) in cis-ApcΔ716/Smad4+/- and cis-ApcΔ716/Smad4+/- KrasG12D mice promoted development of colon tumors that were largely resistant to anti-VEGF treatment. The myeloid growth factor G-CSF was markedly increased in the serum after induction of colitis. Antibodies blocking G-CSF, or its target Bv8/PROK2, suppressed tumor progression and myeloid cell infiltration when combined with anti-VEGF in CIC-associated CRC and in anti-VEGF-resistant CRC liver metastasis models. In a series of CRC specimens, tumor-infiltrating neutrophils strongly expressed Bv8/PROK2. CRC patients had significantly higher plasma Bv8/PROK2 levels than healthy volunteers and high plasma Bv8/PROK2 levels were inversely correlated with overall survival. Our findings establish Bv8/PROK2 as a translational target in CRC, in combination with anti-VEGF agents. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
