傷口滲液被認(rèn)為通過誘發(fā)瘢痕組織炎癥反應(yīng)而參與腫瘤局部復(fù)發(fā)。由于早期乳腺癌局部復(fù)發(fā)大多位于瘢痕組織，已有學(xué)者對局部放療（例如術(shù)中放療）是否比術(shù)后放療更有效地抑制局部腫瘤復(fù)發(fā)開展臨床研究。此外，目前已知上皮→間質(zhì)轉(zhuǎn)化過程對于促進(jìn)上皮來源癌癥轉(zhuǎn)移發(fā)揮關(guān)鍵作用。

　　2019年5月27日，英國《自然》旗下《科學(xué)報(bào)告》在線發(fā)表波蘭癌癥中心、波茲南醫(yī)科大學(xué)、綠山城大學(xué)、波蘭洗禮紀(jì)念碑醫(yī)院的研究報(bào)告，探討了術(shù)中放療減少傷口滲液誘發(fā)腫瘤潛力的機(jī)制。

　　該研究假設(shè)患者術(shù)后滲液可以激活細(xì)胞的放療旁觀者效應(yīng)（又稱輻射旁效應(yīng)：由受照射細(xì)胞產(chǎn)生的信號或效應(yīng)物質(zhì)引發(fā)旁側(cè)鄰近未受照細(xì)胞出現(xiàn)類似輻射生物效應(yīng)，例如基因突變、微核、細(xì)胞凋亡等）從而改變腫瘤微環(huán)境。為了證實(shí)該假設(shè)，該研究從單純保乳手術(shù)、保乳手術(shù)＋術(shù)中放療患者收集傷口滲液，或者將保乳手術(shù)患者傷口滲液和放療旁觀者效應(yīng)培養(yǎng)基，與原發(fā)性激素受體陽性乳腺癌細(xì)胞（MCF7）和轉(zhuǎn)移性乳腺癌細(xì)胞（MDA-MB-468）一起培養(yǎng)，觀察轉(zhuǎn)移能力、上皮→間質(zhì)轉(zhuǎn)化過程、腫瘤干細(xì)胞表現(xiàn)型的變化，以確定傷口滲液對乳腺癌細(xì)胞轉(zhuǎn)移的可能作用。

　　結(jié)果發(fā)現(xiàn)，傷口滲液可以激發(fā)乳腺癌細(xì)胞的腫瘤干細(xì)胞表現(xiàn)型和上皮→間質(zhì)轉(zhuǎn)化過程。當(dāng)這些細(xì)胞與來自保乳手術(shù)＋術(shù)中放療患者傷口滲液一起培養(yǎng)時(shí)，該作用被部分消除。此外，該研究還證實(shí)了放療旁觀者效應(yīng)對于改變傷口滲液誘發(fā)腫瘤干細(xì)胞表現(xiàn)型和上皮→間質(zhì)轉(zhuǎn)化過程的作用。

　　因此，該研究結(jié)果表明，乳腺癌患者術(shù)后傷口滲液可以誘發(fā)上皮→間質(zhì)轉(zhuǎn)化，但是術(shù)中放療通過激活放療旁觀者效應(yīng)可以削弱該作用。

Sci Rep. 2019 May 27. [Epub ahead of print]

Wound fluids collected postoperatively from patients with breast cancer induce epithelial to mesenchymal transition but intraoperative radiotherapy impairs this effect by activating the radiation-induced bystander effect.

Katarzyna Kulcenty, Igor Piotrowski, Karolina Zaleska, Mateusz Wichtowski, Joanna Wróblewska, Dawid Murawa, Wiktoria Maria Suchorska.

Greater Poland Cancer Centre, Poznań, Poland; Poznań University of Medical Sciences, Poznań, Poland; Poznan University Medical Sciences and Greater Poland Cancer Center, Poznan, Poland; University of Zielona Góra, Zielona Góra, Poland; Poland Baptism Monument Hospital, Gniezno, Poland.

Wound fluids (WF) are believed to play a role in the local recurrences by inducing an inflammatory process in scar tissue area. Given that most local relapse in primary breast cancer patients occur within the scar tissue area, researchers have investigated whether localized radiotherapy, such as intraoperative radiotherapy (IORT), could be more effective than postoperative RT in inhibiting local tumor recurrence. The epithelial-mesenchymal transition (EMT) program plays a critical role in promoting metastasis in epithelium-derived carcinoma. Given this background the main aim of the present study was to determine the mechanisms by which IORT decreases the tumorigenic potential of WF. We assumed that postoperative fluids from patients would activate the radiation-induced bystander effect (RIBE) in treated cells, thus altering the tumor microenvironment. To confirm this hypothesis, WF collected from patients after breast conserving surgery (BCS) alone, after BCS followed by IORT treatment or WF from BCS patients together with RIBE medium were incubated with MCF7 and MDA-MB-468 cells. Changes in the CSC phenotype, in EMT program and potential to migrate were performed to determine the possible role of WF on the migration of breast cancer cells. Our findings show that wound fluids stimulate the CSC phenotype and EMT program in breast cancer cell lines. This effect was partially abrogated when the cells were incubated in wound fluids collected from patients after breast-conserving surgery followed by IORT. Additionally, we confirmed the role of radiation-induced bystander effect in altering the properties of the WF to induce the CSC phenotype and EMT program.

DOI: 10.1038/s41598-019-44412-y