Radiosensitivity of Breast Cancer Cells Is Dependent on the Organ Microenvironment.
Radiosensitivity of Breast Cancer Cells Is Dependent on the Organ Microenvironment.
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DOI：
10.3389/fonc.2022.833894
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
远处转移是乳腺癌患者死亡的主要危险因素，其中肺和肝是远处转移常见的部位。正在进行的临床试验正在研究通过放射治疗对这些转移部位进行额外的局部治疗的益处。然而，由于传统体外系统的局限性，人们对组织特异性微环境和对治疗的调节反应知之甚少。通过使用生物基质支架 (BMS) 重建正常器官中细胞外基质的复杂组成，我们选择研究肝和肺器官特异性组织中工程化乳腺癌“转移”的放疗反应。准备肝脏和肺 BMS 用于组织培养。人乳腺癌细胞系在正常组织培养板或涂有基质胶、肝 BMS 和肺 BMS 的组织培养板上传代。进行克隆形成测定以测量不同剂量辐射下的细胞存活率。活性氧 (ROS) 检测法用于测量癌细胞 6 Gy 照射后的 ROS 水平。乳腺细胞系对不同剂量放射治疗的反应受到其体外无细胞微环境的影响。在肝脏 BMS 中生长的乳腺癌细胞比在肺 BMS 中生长的乳腺癌细胞对放射更敏感。在放疗前后，肺和肝 BMS 中培养的乳腺癌细胞的 ROS 水平高于塑料或基质胶板细胞中的 ROS 水平，突显了与周围组织特异性生长因子和细胞因子的相互作用。放疗后，肺和肝 BMS 中的 ROS 显着增加，表明这些位点为辐射诱导的细胞死亡创造了主要环境。乳腺癌转移的治疗反应取决于器官特异性微环境。这些器官中组织微环境之间的相互作用可以确定治疗药物靶点和放射输送的敏感性，以供未来研究使用。
Distant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer “metastases” in liver and lung organ-specific tissues. Liver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells. The response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death. The therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.
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影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN
影响因子：
4.3
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SACHS, RK;CHEN, PL;HLATKY, LR
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HLATKY, LR
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Fodstad, O
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Kobayashi, Hisayuki
影响因子：
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作者：
Crapo, Peter M.;Gilbert, Thomas W.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.