Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding
Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding
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DOI：
10.1158/1078-0432.ccr-07-4453
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发表时间：
2008-03-01
影响因子：
11.5
通讯作者：
Massarut, Samuele
中科院分区：
文献类型：
--
作者：
Belletti, Barbara;Vaidya, Jayant S.;Massarut, Samuele
目的：在明显成功切除乳腺癌后，局部复发的风险仍然很高，主要是在原始肿瘤周围的区域，这表明伤口愈合过程可能有牵连。放射治疗对这种风险的比例降低并不取决于手术的程度，这表明放射治疗除了杀死肿瘤细胞外，还可能影响肿瘤微环境。我们研究了45名患者在保乳手术后24小时内收集的手术伤口液（WF）如何影响正常和乳腺癌细胞的生长和运动，其中20例在手术切除后立即接受了额外的靶向/术中放射治疗（TARGIT）。WF的蛋白质组学特征及其对乳腺癌细胞内信号转导通路的激活的影响也analysed.Results：WF刺激乳腺癌细胞系的增殖，迁移和侵袭。当使用TARGIT治疗患者的液体时，刺激作用几乎完全消失。这些液体显示改变了几种细胞因子的表达，并未能正确刺激激活的一些细胞内信号转导通路，与未经治疗的patients.Conclusions收获的液体相比：TARGIT的肿瘤床的交付改变了分子组成和生物活性的手术WF。这种新的抗肿瘤作用至少可以部分解释在使用TARGIT的大型试点研究中发现的非常低的复发率，它还为识别新的分子靶点和测试新的治疗药物开辟了一条新的途径。
Purpose: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated. The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment.Experimental Design: We studied how normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted/ntraoperative radioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activation of intracellular signal transduction pathways of breast cancer cells were also analyzed.Results: WF stimulated proliferation, migration, and invasion of breast cancer cell lines. The stimulatory effect was almost completely abrogated when fluids from TARGIT-treated patients were used. These fluids displayed altered expression of several cytokines and failed to properly stimulate the activation of some intracellular signal transduction pathways, when compared with fluids harvested from untreated patients.Conclusions: Delivery of TARGIT to the tumor bed alters the molecular composition and biological activity of surgical WF. This novel antitumoral effect could, at least partially, explain the very low recurrence rates found in a large pilot study using TARGIT It also opens a novel avenue for identifying new molecular targets and testing novel therapeutic agents.