Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, German Red Cross Blood Donor Services, Heidelberg University, Friedrich-Ebert Str. 107, 68167, Mannheim, Germany.
FlowCore Mannheim, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl Str. 13-17, 68167, Mannheim, Germany.
Strahlenther Onkol. 2020 Apr;196(4):398-404. doi: 10.1007/s00066-020-01586-z. Epub 2020 Feb 6.
Mesenchymal stromal cells (MSC) in bone marrow have been shown to be radioresistant, which is related to pronounced DNA repair mechanisms. Intraoperative radiotherapy (IORT) during breast-conserving surgery for early breast cancer is an innovative technique applying low energy x‑ray to the tumor bed immediately after removal of the tumor. IORT is considered to reduce the risk of local tumor recurrence by directly targeting cells of the tumor bed and altering the local microenvironment. Aim of this study was to investigate whether IORT affects the outgrowth potential of breast adipose tissue-derived MSC (bASC) as part of the tumor bed.
After surgical tumor resection, biopsies of the tumor bed were taken before (pre IORT) and after IORT (post IORT) and processed applying well-established protocols for ASC isolation and characterization.
In all, 95% of pre IORT tumor bed samples yielded persistently outgrowing bASC with typical ASC characteristics: fibroblastoid morphology, proliferation, adipogenic and osteogenic differentiation and ASC surface marker expression. However, none of the post IORT samples yielded persistent outgrowth of bASC.
After breast-conserving surgery, approximately 90% of local recurrences emerge in close proximity to the initial tumor bed, potentially reflecting a significant contribution of the tumor bed to relapse. Our data show that IORT, besides the proven effect on breast cancer cells, efficiently modifies the tumor environment by having an impact on tumor bed bASC. This effect on tumor bed stromal cells might contribute to reduce the risk of tumor relapse and metastases.
骨髓间充质干细胞 (MSC) 具有较强的放射抗性，这与其显著的 DNA 修复机制有关。早期乳腺癌保乳手术中的术中放疗 (IORT) 是一种创新技术，在切除肿瘤后立即用低能量 X 射线照射肿瘤床。IORT 被认为通过直接靶向肿瘤床细胞并改变局部微环境来降低局部肿瘤复发的风险。本研究旨在探讨 IORT 是否会影响作为肿瘤床一部分的乳腺脂肪组织来源的间充质干细胞 (bASC) 的体外生长潜力。
在手术切除肿瘤后，在 IORT 前 (IORT 前) 和 IORT 后 (IORT 后) 从肿瘤床取活检，并应用 ASC 分离和鉴定的既定方案进行处理。
所有 IORT 前肿瘤床样本中有 95%持续产生具有典型 ASC 特征的持续生长的 bASC：成纤维细胞样形态、增殖、成脂和成骨分化以及 ASC 表面标志物表达。然而，没有一个 IORT 后样本产生持续生长的 bASC。
保乳手术后，大约 90%的局部复发出现在初始肿瘤床附近，这可能反映了肿瘤床对复发的重要贡献。我们的数据表明，IORT 除了对乳腺癌细胞的已证实作用外，还通过影响肿瘤床 bASC 有效地改变了肿瘤环境。这种对肿瘤床基质细胞的影响可能有助于降低肿瘤复发和转移的风险。
