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• W2000623133 abstract "Breast cancer has a high tendency to metastasize to the bone. Breast cancer bone metastasis causes several serious clinical complications such as extreme bone pain, bone fracture, hypercalcemia, and spinal cord compression. Furthermore, once breast cancer metastasizes to the bone, it often becomes incurable. However, the molecular mechanism of breast cancer bone metastasis is not fully understood. CXCR3 and its ligands (CXCL9, CXCL10 and CXCL11) have been shown to play a role in the initiation and progression of cancer metastasis in various types of cancer including breast cancer. Specifically, it has been demonstrated that CXCR3 can promote breast cancer cell line metastasis to the lung in mouse models. A recent study has revealed that CXCR3 is highly expressed in breast cancer tissues and that its expression is positively associated with breast cancer progression. Since the bone is the most common site of breast cancer metastasis, it is possible that CXCR3 and one or more of its ligands are also involved in breast cancer bone metastasis by promoting extravasation of breast tumor cells to the bone. The objective of this study was to carry out several experiments to test this possibility. First, we assessed whether MDA-MB-231 breast cancer cell line expresses CXCR3 using RT-PCR and Western blot analysis. Our data indicate that both CXCR3 mRNA and protein are highly expressed in MDA-MB-231 cells. Next, the expression of CXCR3 ligands (CXCL9, CXCL10, and CXCL11) in bone cells (RAW264.7 and RAW264.7-derived osteoclasts) was examined using RT-PCR, and the data indicate that the bone cells express CXCL10 and CXCL11. In particular, CXCL11 mRNA expression levels increase during osteoclast differentiation. Finally, we performed chemotaxis assays to determine whether the bone cells are able to induce directed migration of MDA-MB-231 cells. We found that the bone cells can exert profound chemotactic effects on MDA-MB-231 cells. Taken together, these findings support the possibility that CXCR3 and its ligands may be involved in breast cancer bone metastasis by mediating breast cancer cell extravasation into the bone marrow. Future studies are needed to address whether CXCR3 is the predominant factor in mediating bone cell-dependent breast cancer migration. Moreover, animal model studies are also needed to investigate whether CXCR3 and its ligands are involved in breast cancer bone metastasis in vivo. If CXCR3 is in fact a predominant factor mediating breast cancer metastasis, CXCR3 may be a potential therapeutic target of breast cancer metastasis.Citation Format: Wendy Feng, Tino Unlap. Potential role of CXCR3 in breast cancer bone metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B51." @default.
• W2000623133 created "2016-06-24" @default.
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• W2000623133 date "2013-02-01" @default.
• W2000623133 modified "2023-09-25" @default.
• W2000623133 title "Abstract B51: Potential role of CXCR3 in breast cancer bone metastasis" @default.
• W2000623133 doi "https://doi.org/10.1158/1538-7445.tim2013-b51" @default.
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