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Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

Lynn Feys (UGent) , Benedicte Descamps (UGent) , Christian Vanhove (UGent) , Anne Vral (UGent) , Liv Veldeman (UGent) , Stefan Vermeulen, Carlos De Wagter (UGent) , Marc Bracke (UGent) and Olivier De Wever (UGent)
(2015) ONCOTARGET. 6(29). p.26615-26632
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Abstract
Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.
Keywords
radiotherapy, triple-negative breast cancer, CXCL12, MIF, AMD3100, CHEMOKINE RECEPTOR CXCR4, TUMOR-GROWTH, RANDOMIZED-TRIALS, RESEARCH PLATFORM, LOCAL RECURRENCE, BONE-MARROW, DNA-DAMAGE, RADIOTHERAPY, CELLS, IRRADIATION

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Chicago
Feys, Lynn, Benedicte Descamps, Christian Vanhove, Anne Vral, Liv Veldeman, Stefan Vermeulen, Carlos De Wagter, Marc Bracke, and Olivier De Wever. 2015. “Radiation-induced Lung Damage Promotes Breast Cancer Lung-metastasis Through CXCR4 Signaling.” Oncotarget 6 (29): 26615–26632.
APA
Feys, L., Descamps, B., Vanhove, C., Vral, A., Veldeman, L., Vermeulen, S., De Wagter, C., et al. (2015). Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling. ONCOTARGET, 6(29), 26615–26632.
Vancouver
1.
Feys L, Descamps B, Vanhove C, Vral A, Veldeman L, Vermeulen S, et al. Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling. ONCOTARGET. 2015;6(29):26615–32.
MLA
Feys, Lynn, Benedicte Descamps, Christian Vanhove, et al. “Radiation-induced Lung Damage Promotes Breast Cancer Lung-metastasis Through CXCR4 Signaling.” ONCOTARGET 6.29 (2015): 26615–26632. Print.
@article{6990041,
  abstract     = {Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10\%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. 
Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.},
  author       = {Feys, Lynn and Descamps, Benedicte and Vanhove, Christian and Vral, Anne and Veldeman, Liv and Vermeulen, Stefan and De Wagter, Carlos and Bracke, Marc and De Wever, Olivier},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  language     = {eng},
  number       = {29},
  pages        = {26615--26632},
  title        = {Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling},
  url          = {http://dx.doi.org/10.18632/oncotarget.5666},
  volume       = {6},
  year         = {2015},
}

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