Abstract A30: FOXP3 regulates metastatic spread of breast cancer via control of expression of CXCR4 chemokine receptor

• Published in: Cancer prevention research (Philadelphia, Pa.) Pa.), 2010-12, Vol.3 (12_Supplement), p.A30-A30
• Main Authors: Overbeck-Zubrzycka, Dorota, Kirby, John A., Ali, Simi, Lennard, Thomas WJ
• Format: Article
• Language: English
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.PREV-10-A30

Background: The transcription factor FOXP3 can regulate T cell migration by inhibiting expression of CXCR4, the receptor for the chemokine CXCL12. The increased expression of CXCR4 by breast cancer cells can drive metastatic migration towards sites which express CXCL12. Intracellular trafficking of FOXP3 to the nucleus is required in order for this protein to function. There are three distinct Foxp3 domains that contribute to its nuclear transport. Importantly, human T-cells express at least two splice variants of FOXP3 protein what may affect the structure of nuclear localization regions. We hypothesized that FOXP3 is inactivated in breast cancer due to dysfunctional FOXP3 isoforms causing failure of nuclear localization with subsequent increase in CXCR4 and development of metastasis. Methods: The expression patterns of FOXP3 and CXCR4 were measured at mRNA (qPCR) and protein (immunohistochemistry, immunofluorescence, FACS) levels. 100 sections of benign tissue, cancers, lymph node metastases and 7 breast cell lines were examined with traditional and digital microscopy techniques. The results were correlated with pathological and clinical prognostic indicators of breast cancer. Following comparison of FOXP3 sequences of cancer and normal cells, cancer cells were transfected with FOXP3 vector and changes in their chemotaxis and invasion were investigated. Results: Normal breast epithelial cells (both patient-derived tissues and laboratory cultured cell lines) expressed FOXP3 in their nuclei and at the same time fail to express CXCR4. Breast cancer cells significantly (p