Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer.

Published

Journal Article

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy.

Full Text

Duke Authors

Cited Authors

  • Xu, L; Duda, DG; di Tomaso, E; Ancukiewicz, M; Chung, DC; Lauwers, GY; Samuel, R; Shellito, P; Czito, BG; Lin, P-C; Poleski, M; Bentley, R; Clark, JW; Willett, CG; Jain, RK

Published Date

  • October 15, 2009

Published In

Volume / Issue

  • 69 / 20

Start / End Page

  • 7905 - 7910

PubMed ID

  • 19826039

Pubmed Central ID

  • 19826039

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-2099

Language

  • eng

Conference Location

  • United States