Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis.

Abstract:

:The increase of interleukin-4 (IL-4) level in tumor environment and the up-regulation of IL-4 receptor (IL-4R) on tumor cells have been long observed. However, their significance for tumor development has not been investigated. Here, we found that endogenous IL-4 promotes tumor growth because neutralizing IL-4 by 11B11 monoclonal antibody (mAb) significantly delayed the growth of MCA205 fibrosarcoma. We also observed that tumor cells with higher IL-4R expression have more chances to survive in immunocompetent mice. To investigate how endogenous IL-4 influences tumor growth, we established a pair of tumor cells with or without IL-4R expression from the common parental cells. IL-4R-competent tumors exhibit increased growth compared with its IL-4R-deficient counterparts when inoculated into syngeneic mice. This growth advantage was still kept in IL-4R knockout mice but was abrogated in mice given i.p. with IL-4 neutralizing mAb. In vitro analyses indicate that IL-4 neither affects the proliferation of tumor cells nor changes the expression of several immune-related molecules, such as MHC-I, Fas, and B7-H3. Nonetheless, IL-4 up-regulates antiapoptotic gene expression in tumor cells and reduces apoptosis of tumor cells in vivo, as evidenced by real-time PCR, immunoblotting, and TUNEL staining. These findings were helpful to understand the long clinical observation and revealed that endogenous IL-4, the product of host immune response, can be used by tumor cells to facilitate their growth.

journal_name

Cancer Res

journal_title

Cancer research

authors

Li Z,Jiang J,Wang Z,Zhang J,Xiao M,Wang C,Lu Y,Qin Z

doi

10.1158/0008-5472.CAN-08-0449

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

8687-94

issue

21

eissn

0008-5472

issn

1538-7445

pii

68/21/8687

journal_volume

68

pub_type

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