Centre de Recherche en Radiothérapie, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Int J Radiat Biol. 2011 May;87(5):472-82. doi: 10.3109/09553002.2011.542541. Epub 2011 Jan 13.
Treatment of breast tumours frequently involves irradiating the whole breast to reach malignant microfoci scattered throughout the breast. In this study, we determined whether irradiation of normal tissues could increase the invasiveness of breast cancer cells in a mouse model.
Non-irradiated MC7-L1 mouse mammary carcinoma cells were injected subcutaneously in irradiated and non-irradiated thighs of Balb/c mice. The invasion volume, tumour volume, blood vessel permeability and interstitial volumes were monitored by magnetic resonance imaging (MRI). Slices of normal tissue invaded by cancer cells were examined by histology. Activity of matrix metalloproteinase -2 and -9 (MMP -2 and -9) in healthy and irradiated tissues was determined, and the proliferation index of the invading cancer cells was evaluated.
Three weeks after irradiation, enhancement of MC7-L1 cells invasiveness in irradiated thighs was already detected by MRI. The tumour invasion volume continued to extend 28- to 37-fold compared to the non-irradiated implantation site for the following three weeks, and it was associated with an increase of MMP-2 and -9 activities in healthy tissues. The interstitial volume associated with invading cancer cells was significantly larger in the pre-irradiated sites; while the blood vessels permeability was not altered. Cancer cells invading the healthy tissues were proliferating at a lower rate compared to non-invading cancer cells.
Implantation of non-irradiated mammary cancer cells in previously irradiated normal tissue enhances the invasive capacity of the mammary cancer cells and is associated with an increased activity of MMP-2 and -9 in the irradiated normal tissue.
治疗乳房肿瘤通常需要对整个乳房进行放射治疗，以达到散布在乳房中的恶性微焦点。在这项研究中，我们确定了在小鼠模型中，照射正常组织是否会增加乳腺癌细胞的侵袭性。
将未照射的 MC7-L1 小鼠乳腺癌细胞皮下注射到照射和未照射的 Balb/c 小鼠大腿中。通过磁共振成像（MRI）监测侵袭体积、肿瘤体积、血管通透性和间质体积。通过组织学检查检查被癌细胞侵袭的正常组织切片。测定健康和照射组织中基质金属蛋白酶-2 和 -9（MMP-2 和 -9）的活性，并评估侵袭性癌细胞的增殖指数。
照射后 3 周，通过 MRI 已经检测到 MC7-L1 细胞在照射大腿中的侵袭性增强。肿瘤侵袭体积在接下来的 3 周内继续扩展 28-37 倍，与非照射植入部位相比，并且与健康组织中 MMP-2 和 -9 活性的增加相关。与侵袭性癌细胞相关的间质体积在前照射部位明显更大；而血管通透性没有改变。与非侵袭性癌细胞相比，侵袭健康组织的癌细胞增殖速度较低。
将未照射的乳腺癌细胞植入先前照射的正常组织中会增强乳腺癌细胞的侵袭能力，并与照射正常组织中 MMP-2 和 -9 的活性增加相关。
