Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
Department of Radiation Oncology, University Hospital of North Norway, Tromsø, Norway.
Cancer Rep (Hoboken). 2024 Mar;7(3):e2018. doi: 10.1002/cnr2.2018.
Cancer-associated fibroblasts (CAFs) consist of heterogeneous connective tissue cells and are often constituting the most abundant cell type in the tumor stroma. Radiation effects on tumor stromal components like CAFs in the context of radiation treatment is not well-described.
This study explores potential changes induced by ionizing radiation (IR) on platelet-derived growth factor (PDGF)/PDGFRs and transforming growth factor-beta (TGF-β)/TGFβRs signaling systems in CAFs.
Experiments were carried out by employing primary cultures of human CAFs isolated from freshly resected non-small cell lung carcinoma tumor tissues. CAF cultures from nine donors were treated with one high (1 × 18 Gy) or three fractionated (3 × 6 Gy) radiation doses. Alterations in expression levels of TGFβRII and PDGFRα/β induced by IR were analyzed by western blots and flow cytometry. In the presence or absence of cognate ligands, receptor activation was studied in nonirradiated and irradiated CAFs. Radiation exposure did not exert changes in expression of PDGF or TGF-β receptors in CAFs. Additionally, IR alone was unable to trigger activation of either receptor. The radiation regimens tested did not affect PDGFRβ signaling in the presence of PDGF-BB. In contrast, signaling via pSmad2/3 and pSmad1/5/8 appeared to be down-regulated in irradiated CAFs after stimulation with TGF-β, as compared with controls.
Our data demonstrate that IR by itself is insufficient to induce measurable changes in PDGF or TGF-β receptor expression levels or to induce receptor activation in CAFs. However, in the presence of their respective ligands, exposure to radiation at certain doses appear to interfere with TGF-β receptor signaling.
癌症相关成纤维细胞（CAFs）由异质的结缔组织细胞组成，通常构成肿瘤基质中最丰富的细胞类型。在放射治疗中，辐射对肿瘤基质成分（如 CAFs）的影响尚未得到充分描述。
本研究探讨电离辐射（IR）对 CAFs 中血小板衍生生长因子（PDGF）/PDGFRs 和转化生长因子-β（TGF-β）/TGFβRs 信号系统的潜在影响。
通过分离自新鲜切除的非小细胞肺癌肿瘤组织的原代人 CAF 培养物进行实验。用 1 次高剂量（1×18Gy）或 3 次分割剂量（3×6Gy）处理 9 位供体的 CAF 培养物。通过 Western blot 和流式细胞术分析 IR 诱导的 TGFβRII 和 PDGFRα/β表达水平的变化。在存在或不存在同源配体的情况下，研究了非照射和照射 CAF 中的受体激活情况。IR 处理并未改变 CAFs 中 PDGF 或 TGF-β 受体的表达。此外，单独的 IR 无法触发任何一种受体的激活。所测试的放射方案在存在 PDGF-BB 的情况下不会影响 PDGFRβ 信号。相反，与对照相比，刺激 TGF-β 后，照射 CAFs 中的 pSmad2/3 和 pSmad1/5/8 信号似乎被下调。
我们的数据表明，IR 本身不足以诱导 CAFs 中 PDGF 或 TGF-β 受体表达水平的可测量变化，也不能诱导受体激活。然而，在其各自配体存在的情况下，在某些剂量下暴露于辐射似乎会干扰 TGF-β 受体信号。
