Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/11/1816 |
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| author | Guanmin Meng Melinda Wuest Xiaoyun Tang Jennifer Dufour YuanYuan Zhao Jonathan M. Curtis Todd P. W. McMullen David Murray Frank Wuest David N. Brindley |
| author_facet | Guanmin Meng Melinda Wuest Xiaoyun Tang Jennifer Dufour YuanYuan Zhao Jonathan M. Curtis Todd P. W. McMullen David Murray Frank Wuest David N. Brindley |
| author_sort | Guanmin Meng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:59:12Z |
| format | Article |
| id | doaj.art-c0032e74a81944d18cfceefce5f325b0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:59:12Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c0032e74a81944d18cfceefce5f325b02023-09-02T20:03:07ZengMDPI AGCancers2072-66942019-11-011111181610.3390/cancers11111816cancers11111816Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory CycleGuanmin Meng0Melinda Wuest1Xiaoyun Tang2Jennifer Dufour3YuanYuan Zhao4Jonathan M. Curtis5Todd P. W. McMullen6David Murray7Frank Wuest8David N. Brindley9Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, CanadaCancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Oncology, Division of Oncologic Imaging, University of Alberta, Edmonton, AB T6G 2R7, CanadaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, 410 Agriculture/Forestry Centre, 3-60D South Academic Building, Edmonton, AB T6G 2P5, CanadaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, 410 Agriculture/Forestry Centre, 3-60D South Academic Building, Edmonton, AB T6G 2P5, CanadaCancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, CanadaCancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, CanadaCancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, CanadaBreast 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.https://www.mdpi.com/2072-6694/11/11/1816adiponectinadipose tissuebreast cancerchemokinescytokinesradiotherapy |
| spellingShingle | Guanmin Meng Melinda Wuest Xiaoyun Tang Jennifer Dufour YuanYuan Zhao Jonathan M. Curtis Todd P. W. McMullen David Murray Frank Wuest David N. Brindley Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle Cancers adiponectin adipose tissue breast cancer chemokines cytokines radiotherapy |
| title | Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle |
| title_full | Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle |
| title_fullStr | Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle |
| title_full_unstemmed | Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle |
| title_short | Repeated Fractions of X-Radiation to the Breast Fat Pads of Mice Augment Activation of the Autotaxin-Lysophosphatidate-Inflammatory Cycle |
| title_sort | repeated fractions of x radiation to the breast fat pads of mice augment activation of the autotaxin lysophosphatidate inflammatory cycle |
| topic | adiponectin adipose tissue breast cancer chemokines cytokines radiotherapy |
| url | https://www.mdpi.com/2072-6694/11/11/1816 |
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