Abstract P1-05-04: A novel mechanism of epithelial-mesenchymal transition in breast cancer metastasis: Involvement of prostanoid receptor

Autor: Jiawei Chen, Vivian Y. Shin, Man-Ting Siu, Isabella Cheuk, Ava Kwong, J. Ho
Rok vydání: 2016
Předmět:
Zdroj: Cancer Research. 76:P1-05
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.sabcs15-p1-05-04
Popis: Background: Triple-negative breast cancer is associated with higher metastatic rate and poor prognosis than other subtypes of breast cancer due to lack of targeted therapy. Epithelial-mesenchymal transition (EMT) is linked with metastasis with phenotypic conversion of epithelial cells. However, the regulation of EMT in breast cancer metastasis remains largely unstudied. Recent attention has focused on targeting the downstream of COX-2 pathway, understanding the role of prostanoid receptors in breast cancer metastasis may help the development of effective therapeutic interventions for patients with metastasis. Methods: A stable EP2-expression cell line (MB-231-EP2) was used to study tumorigenesis and distant metastasis in human breast cancer metastatic model. Localization of EP2 and EMT markers were examined by immunostaining and immunofluorescence. Profiles of drug transporters genes were compared between siEP2 and siControl cells. Functional role of EP2 on cell proliferation, invasion and apoptosis were assessed. Alteration of EMT markers were examined by real-time PCR and Western blot analysis. Results: Expression of EP2 receptor were higher in human primary tumors than non-tumor tissues. EP2 receptor was predominantly expressed in metastatic tumors than primary tumors in human breast cancer metastatic mice model. The metastatic tumors showed a higher Ki67 (cell proliferation) and CD31 (angiogenesis) than primary tumors in the xenograft tissues. Larger tumors and poor survival were seen in MD-231-EP2 bearing mice when compared with control. Silencing of EP2 by siRNA markedly reduced cell proliferation and invasion, but increased apoptosis and expression of solute carrier family 19 member A3 (SLC19A3) gene. Interestingly, SLC19A3 had a lower expression in primary tumors and was inversely correlated with EP2 expression. Ectopic expression of SLC19A3 suppressed cell proliferation and invasion through the restoration of E-cadherin and other EMT markers (Twist, Zeb1 and Snai2). Immunofluorescence staining showed that the localization of Twist and E-cadherin were altered in siEP2 cells. Conclusion: Our results showed that EP2 promoted EMT and breast cancer metastasis through the downregulation of SLC19A3 expression. Taken together, targeting EP2/SLC19A3 signaling pathway maybe a potential treatment for metastasis and adjuvant chemotherapy to reduce the metastatic risk. Citation Format: Kwong A, Siu MT, Cheuk I, Ho JC, Chen J, Shin VY. A novel mechanism of epithelial-mesenchymal transition in breast cancer metastasis: Involvement of prostanoid receptor. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-05-04.
Databáze: OpenAIRE
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