期刊
CANCER LETTERS
卷 364, 期 2, 页码 106-117出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.04.029
关键词
TSLP; Eosinophils; Cervical cancer cells; CCL17; Proliferation
类别
资金
- National Natural Science Foundation of China (NSFC) [81471513]
- Training Program for Young Talents of Shanghai Health System [XYQ2013104]
- Program for Zhuoxue of Fudan University
- NSFC [81302260]
Cervical cancer is often associated with eosinophil (EOS) infiltration, but the source and the role of EOS are still largely unknown. Our previous work has established that thymic stromal lymphopoietin (TSLP) can stimulate the growth of cervical cancer cell in an autocrine manner. Here, we report that EOS infiltration of the lesion site increased gradually with the progression of cervical cancer. The increase in TSLP secretion in HeLa and SiHa cells induced by hypoxia led to a high level of chemokine CCL17 production by HeLa and SiHa cells, and recruited more EOS to the cancer lesion. In addition, TSLP derived from HeLa and SiHa cells promoted proliferation, up-regulated the levels of anti-inflammatory cytokines (IL-10, IL-4, IL-5 and IL-13), and decreased the expression of CD80 and CD86 of EOS. Such educated EOS significantly promoted proliferation and restricted the apoptosis of cervical cancer cells, which was associated with the up-regulation of Ki-67, PCNA and Bcl-2, and the down-regulation of Fas and FasL in HeLa and SiHa cells. These results suggest that a high level of TSLP in cancer lesions mediated by hypoxia is an important regulator of the progression of cervical cancer by recruiting and licensing tumor-associated EOS to promote the growth of the cervical cancer cell itself. This provides a scientific basis on which potential therapeutic strategies could be targeted to cervical cancer, especially for patients with massive infiltrations of EOS. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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