Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle

Cancers

David Murray¹  Melinda Wuest¹  ToddP. W. McMullen¹  Frank Wuest¹  JonathanM. Curtis²  YuanYuan Zhao²  DavidN. Brindley³  Xiaoyun Tang³  Guanmin Meng³  Jennifer Dufour⁴ 

[1] Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada;Department of Agricultural, Food and Nutritional Science, University of Alberta, 410 Agriculture/Forestry Centre, 3-60D South Academic Building, Edmonton, AB T6G 2P5, Canada;Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada;Department of Oncology, Division of Oncologic Imaging, University of Alberta, Edmonton, AB T6G 2R7, Canada;

关键词: adiponectin;    adipose tissue;    breast cancer;    chemokines;    cytokines;    radiotherapy;   

DOI  :  10.3390/cancers11111816

来源: DOAJ

【 摘 要 】

Breast cancer patients are usually treated with multiple fractions of radiotherapy (RT) to the whole breast after lumpectomy. We hypothesized that repeated fractions of RT would progressively activate the autotaxin−lysophosphatidate-inflammatory cycle. To test this, a normal breast fat pad and a fat pad containing a mouse 4T1 tumor were irradiated with X-rays using a small-animal “image-guided” RT platform. A single RT dose of 7.5 Gy and three daily doses of 7.5 Gy increased ATX activity and decreased plasma adiponectin concentrations. The concentrations of IL-6 and TNFα in plasma and of VEGF, G-CSF, CCL11 and CXCL10 in the irradiated fat pad were increased, but only after three fractions of RT. In 4T1 breast tumor-bearing mice, three fractions of 7.5 Gy augmented tumor-induced increases in plasma ATX activity and decreased adiponectin levels in the tumor-associated mammary fat pad. There were also increased expressions of multiple inflammatory mediators in the tumor-associated mammary fat pad and in tumors, which was accompanied by increased infiltration of CD45+ leukocytes into tumor-associated adipose tissue. This work provides novel evidence that increased ATX production is an early response to RT and that repeated fractions of RT activate the autotaxin−lysophosphatidate-inflammatory cycle. This wound healing response to RT-induced damage could decrease the efficacy of further fractions of RT.

【 授权许可】

Unknown