Radiobiology Laboratory, Greater Poland Cancer Centre, Garbary 15 Street, 61-866 Poznań, Poland.
Department of Electroradiology, Poznań University of Medical Sciences, Garbary 15 Street, 61-866 Poznań, Poland.
Int J Mol Sci. 2020 Feb 10;21(3):1159. doi: 10.3390/ijms21031159.
In patients with breast cancer who undergo breast-conserving surgery (BCS), more than 90% of local recurrences occur in the same quadrant as the primary cancer. Surgical wound fluids (SWF) are believed to play a role in this process by inducing an inflammatory process in the scar tissue area. Despite strong clinical data demonstrating the benefits of intraoperative radiotherapy (IORT), the biological basis underlying this process remains poorly understood. Ionizing radiation (IR) directly affects cells by damaging DNA, thereby altering the cell phenotype. IR directly affects cancer cells and also influences unirradiated cells located nearby, a phenomenon known as the radiation-induced bystander effect (RIBE), significantly modifying the tumor microenvironment. We hypothesized that SWF obtained from patients after BCS and IORT would induce a radiobiological response (due to RIBE) in unirradiated cells, thereby modifying their phenotype. To confirm this hypothesis, breast cancer cells were incubated with SWF collected from patients after BCS: (1) without IORT (wound fluid (WF) group), (2) with IORT (radiotherapy wound fluid (RT-WF) group), and (3) WF with conditioned medium from irradiated cells (WF+RIBE group) and then subjected to microarray analysis. We performed gene set enrichment analysis to determine the biological processes present in these cells. This analysis showed that the RT-WF and WF+RIBE groups shared common biological processes, including the enhancement of processes involved in cell-cycle regulation, DNA repair, and oxidative phosphorylation. The WF group was characterized by overrepresentation of pathways involved in the INF-α and INF-γ response, inflammatory response, and the IL6 JAK/STAT3 signaling pathway. These findings show that MDA-MB-468 cells stimulated with surgical wound fluids obtained from patients who underwent BCS plus IORT and from cells stimulated with SWF plus RIBE share common biological processes. This confirms the role of the radiation-induced bystander effect in altering the biological properties of wound fluids.
在接受保乳手术 (BCS) 的乳腺癌患者中，超过 90%的局部复发发生在原发性癌症的同一象限。手术伤口液 (SWF) 被认为在这个过程中起作用，通过在疤痕组织区域诱导炎症过程。尽管有强有力的临床数据表明术中放疗 (IORT) 的益处，但这一过程的生物学基础仍知之甚少。电离辐射 (IR) 通过损伤 DNA 直接影响细胞，从而改变细胞表型。IR 直接影响癌细胞，也影响附近未受照射的细胞，这种现象称为辐射诱导的旁观者效应 (RIBE)，显著改变肿瘤微环境。我们假设从接受 BCS 和 IORT 的患者中获得的 SWF 会在未受照射的细胞中引起放射生物学反应 (由于 RIBE)，从而改变它们的表型。为了证实这一假设，将乳腺癌细胞与从接受 BCS 后的患者中收集的 SWF 孵育：(1) 没有 IORT（伤口液 (WF) 组），(2) 有 IORT（放疗伤口液 (RT-WF) 组）和 (3) 用辐照细胞的条件培养基孵育的 WF (WF+RIBE 组），然后进行微阵列分析。我们进行了基因集富集分析，以确定这些细胞中存在的生物学过程。该分析表明，RT-WF 和 WF+RIBE 组具有共同的生物学过程，包括增强与细胞周期调控、DNA 修复和氧化磷酸化相关的过程。WF 组的特点是涉及 INF-α 和 INF-γ 反应、炎症反应和 IL6 JAK/STAT3 信号通路的途径过表达。这些发现表明，用从接受 BCS 加 IORT 的患者获得的手术伤口液刺激的 MDA-MB-468 细胞和用 SWF 加 RIBE 刺激的细胞具有共同的生物学过程。这证实了辐射诱导的旁观者效应在改变伤口液的生物学特性中的作用。
