Vascular Endothelial Growth Factor Mediates the Sprouted Axonogenesis of Breast Cancer in Rat

作者全名："Han, Hongxiu; Yang, Chunxue; Zhang, Yuan; Han, Changhao; Zhang, Guohua"

作者地址："[Han, Hongxiu] Tongji Univ, Tongji Hosp, Dept Pathol, 389 Xincun Rd, Shanghai 200065, Peoples R China; [Han, Hongxiu; Yang, Chunxue; Zhang, Yuan] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Pathol, Shanghai, Peoples R China; [Zhang, Guohua] Shanghai Jiao Tong Univ, Sch Med, Dept Anat & Physiol, 280 S Chongqing Rd, Shanghai 200025, Peoples R China; [Han, Changhao] Chongqing Med Univ, Clin Med Coll 2, Dept Clin Med, Chongqing, Peoples R China"

通信作者："Han, HX (corresponding author), Tongji Univ, Tongji Hosp, Dept Pathol, 389 Xincun Rd, Shanghai 200065, Peoples R China.; Zhang, GH (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Dept Anat & Physiol, 280 S Chongqing Rd, Shanghai 200025, Peoples R China."

来源：AMERICAN JOURNAL OF PATHOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000632503000009

JCR分区：Q1

影响因子：6

年份：2021

卷号：191

期号：3

开始页：515

结束页：526

文献类型：Article

关键词：　

摘要："Nerve infiltration into the tumor is a common feature of the tumor microenvironment. The mechanisms of axonogenesis in breast cancer remain unclear. We hypothesized that vascular endothelial growth factor (VEGF), as well as nerve growth factor (NGF), is involved in the axonogenesis of breast cancer. A N-methyl-N-nitrosourea (MNU)-induced rat model of breast cancer was used to explore the presence of axonogenesis in breast tumor and the involvement of VEGF, as well as NGF, in the axonogenesis of breast tumor. Nerve infiltration into the tumor was found in MNU-induced rat model of breast cancer including the sensory and sympathetic nerve fibers. Nerve density was increased following the growth of tumor. The sensory neurons innervating the thoracic and abdominal mammary tumors peaked at T5 to T6 and L1 to L2 dorsal root ganglions, respectively. Either VEGF receptor inhibitor or antibody against VEGF receptor 2, as well as NGF receptor inhibitor, apparently decreased both the nerve density and vascular density of breast tumor. The reduced nerve density was correlated with the decreased vascular density induced by these treatments. In cultured dorsal root ganglion neurons, phosphatidylinositol 3 (PI3K)/Akt, extracellular signal-regulated protein kinase (ERK), and p38 inhibitors significantly attenuated VEGF-induced neurite elongation. These findings provide direct evidence that VEGF, as well as NGF, may control the axonogenesis of breast cancer."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770533, 81070891, 81272927]"

基金资助正文："Supported by National Natural Science Foundation of China grants 81770533, 81070891 (G.Z.), and 81272927 (H.H.)."