الفهرس Only 14 pages are availabe for public view
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Abstract
Elevated plamsacytoid dendritic cells (PDCs) infiltration into breast cancer tissues has been reported to be associated with poor prognosis, shorter overall and relapse-free survival rate. CXCR4/SDF-1 axis is a central chemokine axis contributing to lymph node metastasis in breast cancer. The aim of the present study was to investigate whether PDCs may contribute to lymph node metastasis through CXCR4 and to identify the underlying molecular mechanisms. We assessed PDCs infiltration into breast cancer tissues of positive lymph node (pLN) and negative lymph nodes (nLN) patients by immunostaining of CD303+ cells. In addition, CXCR4+cells percentages in breast carcinoma tissues were counted by flow cytometry. PDCs were immuno-magnetically isolated from axillary tributaries during modified radical mastectomy and cultured overnight to produce media conditioned by PDCs secrotome. The human breast cancer cell lines SKBR3 and MCF-7 were employed to test the effect of PDCs secretome on CXCR4 expression. Also, we quantified the expression of SDF-1 in lymph nodes of both groups. We found that breast carcinoma tissues of pLN breast cancer patients have higher PDCs infiltration than those of nLN ones. Also, we showed that the breast cancer tissues of pLN patients encompasses more CXCR4+cells than those of nLN patients. Interestingly, we found that SDF-1 is highly expressed on lymph nodes metastases. Quantitative PCR results indicated a significant upregulation of mRNA expression of TNF-Ü in pLN patients’ PDCs. Mechanistically, expression of CXCR4 was upregulated, in parallel with NF-{u03F0}B upregulation, in MCF-7 and SKBR-3 cell lines upon stimulation with secretome of PDCs isolated from pLN patients compared to nLN patients. In conclusion, our study suggests a potential role for PDCs in lymph node metastasis via CXCR4/SDF-1 axis, which could be therapeutically targeted to hamper breast cancer metastasis