Unknown

Dataset Information

0

NF-?B signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells.


ABSTRACT: The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells. Treatment of 4T1 cells with CXCL10 increased the expression of P65, a subunit of the NF-?B pathway, via activation of the NF-?B transcriptional activity. Ectopic overexpression of P65 increased CXCL10 secretion and blunted JN-2-induced suppression of CXCL10 secretion, whereas overexpression of I?B? suppressed CXCL10 secretion. These results indicate that the CXCL10/CXCR3 axis creates a positive feedback loop through the canonical NF-?B signaling pathway in 4T1 cells. In addition, treatment of osteoblasts with conditioned medium from JN-2-treated 4T1 cells inhibited the expression of RANKL, a crucial cytokine for osteoclast differentiation, which resulted in an inhibitory effect on osteoclast differentiation in the co-culture system of bone marrow-derived macrophages and osteoblasts. Direct intrafemoral injection of 4T1 cells induced severe bone destruction; however, this effect was suppressed by the CXCR3 antagonist via downregulation of P65 expression in an animal model. Collectively, these results suggest that the CXCL10/CXCR3-mediated NF-?B signaling pathway plays a role in the control of autonomous regulation of CXCL10 and malignant tumor properties in breast cancer 4T1 cells.

SUBMITTER: Jin WJ 

PROVIDER: S-EPMC5336559 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

NF-κB signaling regulates cell-autonomous regulation of CXCL10 in breast cancer 4T1 cells.

Jin Won Jong WJ   Kim Bongjun B   Kim Darong D   Park Choo Hea-Young HY   Kim Hong-Hee HH   Ha Hyunil H   Lee Zang Hee ZH  

Experimental & molecular medicine 20170217 2


The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibit  ...[more]

Similar Datasets

| S-EPMC3075605 | biostudies-other
2023-05-10 | PXD039305 | Pride
| S-EPMC7763959 | biostudies-literature
| S-EPMC3532050 | biostudies-other
| S-EPMC8438213 | biostudies-literature
2021-04-17 | GSE172183 | GEO
| S-EPMC3193404 | biostudies-other
| S-EPMC7181720 | biostudies-literature
| S-EPMC4924384 | biostudies-literature
| S-EPMC5241669 | biostudies-literature