Wound fluids affect miR-21, miR-155 and miR-221 expression in breast cancer cell lines, and this effect is partially abrogated by intraoperative radiation therapy treatment

Breast cancer is the most common malignant disease occurring in women. Conservative breast cancer surgery followed by radiation therapy is currently the standard treatment for this type of cancer. The majority of metastases occur within the scar, which initiated a series of studies. As a result, clinical trials aimed to assess whether localized radiotherapy, as intraoperative radiotherapy (IORT), may more effective in inhibiting the formation of local recurrence compared with the standard postoperative whole breast radiotherapy. The present study determined the role of postoperative wound fluids (WFs) from patients diagnosed with breast cancer subsequent to breast conserving surgery or breast conserving surgery followed by IORT on the expression of three microRNAs (miRNAs), consisting of miR-21, miR-155 and miR-221, in distinct breast cancer cell lines that represent the general subtypes of breast cancer. It was determined that the miRNAs responsible for breast cancer progression, induction of tumorigenesis and enrichment of the cancer stem cell phenotype, which is responsible for resistance to tumor therapy, were highly upregulated in the human epidermal growth factor receptor 2-positive breast cancer SK-BR-3 cell line following stimulation with WFs. It is worth emphasizing, that those changes were more significant in WFs collected from patients after surgery alone. The BT-549 cell line showed altered expression only of miR-155 following incubation with WFs. Notably, this change was not associated with IORT. Additionally, it was indicated that both WFs and RT-WF strongly downregulated the expression of miR-21, miR-155 and miR-221 in basal/epithelial and luminal subtypes of breast cancer. It was concluded that the present study contributes to an increased understanding of the role of surgical WFs and IORT treatment in the regulation of miRNA expression. This may enable the development of the current knowledge of breast cancer biology subsequent to IORT treatment and substantially to improve the therapy in the future.