Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates SDF1α, CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with Rectal Cancer

被引：134

作者：

Xu, Lei

Duda, Dan G.

di Tomaso, Emmanuelle

Ancukiewicz, Marek

Chung, Daniel C. ^{[2
]}

Lauwers, Gregory Y. ^{[3
]}

Samuel, Rekha ^{[3
]}

Shellito, Paul ^{[4
]}

Czito, Brian G. ^{[6
]}

Lin, Pei-Chun

Poleski, Martin ^{[7
]}

Bentley, Rex ^{[8
]}

Clark, Jeffrey W. ^{[5
]}

Willett, Christopher G. ^{[6
]}

Jain, Rakesh K. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, EL Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA

[5] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA

[6] Duke Univ, Med Ctr, Div Radiat Oncol, Durham, NC 27710 USA

[7] Duke Univ, Med Ctr, Dept Gastroenterol, Durham, NC 27710 USA

[8] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 20期

关键词：

ENDOTHELIAL GROWTH-FACTOR; CELL-MIGRATION; ANGIOGENESIS; VASCULATURE; RESISTANCE; EXPRESSION; THERAPY;

D O I：

10.1158/0008-5472.CAN-09-2099

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 1 alpha. (SDF1 alpha), its receptor CXCR4, and CXCL6, and down-regulated PIGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1 alpha 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. [Cancer Res 2009;69(20):7905-10]

引用

页码：7905 / 7910

页数：6

共 20 条

[1] AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients [J].