Pre-irradiation of mouse mammary gland stimulates cancer cell migration and development of lung metastases.
Pre-irradiation of mouse mammary gland stimulates cancer cell migration and development of lung metastases.
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DOI：
10.1038/bjc.2013.502
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发表时间：
2013-10-01
影响因子：
8.8
通讯作者：
Paquette, B.
中科院分区：
文献类型：
--
作者：
Bouchard, G.;Bouvette, G.;Therriault, H.;Bujold, R.;Saucier, C.;Paquette, B.
在大多数乳腺癌患者中，放疗诱导炎症，其特征在于肿瘤周围健康组织中的促迁移因子增加。然而，它们在迁移表型的出现和转移形成中的作用仍不清楚。用6戈伊的4次剂量照射BALB/c小鼠的单个乳腺，每次间隔24小时。在最后一次照射后，收集治疗和对照乳腺用于定量促迁移和促炎因子，或植入表达荧光泛素化细胞周期指示剂（FUCCI）的小鼠乳腺癌D2 A1细胞。通过光学成像监测乳腺癌细胞的迁移。在第21天，收集乳腺肿瘤和肺用于组织学分析和转移的定量。乳腺的预照射增加了1.8倍的癌细胞的迁移，2倍的循环癌细胞的数量和2.4倍的肺转移的数量。这些不良反应与白细胞介素-6（IL-6）和环氧合酶-2（考克斯-2）的诱导有关。转移表型的出现被认为与癌细胞中突变的积累有关。我们的研究结果表明，一种替代机制的基础上，从照射乳腺的促迁移因子。在临床上，可以通过抗炎药物来阻止放射诱导的癌细胞迁移，从而提高放射治疗的效率。
In most patients with breast cancer, radiotherapy induces inflammation that is characterised by an increase of promigratory factors in healthy tissues surrounding the tumour. However, their role in the emergence of the migration phenotype and formation of metastases is still unclear. A single mammary gland of BALB/c mice was irradiated with four doses of 6 Gy given at a 24-h interval. After the last session of irradiation, treated and control mammary glands were either collected for quantification of promigratory and proinflammatory factors or were implanted with fluorescent ubiquitination-based cell cycle indicator (FUCCI)-expressing mouse mammary cancer D2A1 cells. The migration of cancer cells in the mammary glands was monitored by optical imaging. On day 21, mammary tumours and lungs were collected for histology analyses and the quantification of metastases. Pre-irradiation of the mammary gland increased by 1.8-fold the migration of cancer cells, by 2-fold the quantity of circulating cancer cells and by 2.4-fold the number of lung metastases. These adverse effects were associated with the induction of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). The emergence of the metastasis phenotype is believed to be associated with the accumulation of mutations in cancer cells. Our results suggest an alternative mechanism based on promigratory factors from irradiated mammary glands. In clinic, the efficiency of radiotherapy could be improved by anti-inflammatory agents that would prevent the stimulation of cancer cell migration induced by radiation.
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影响因子：
2.5
作者：
Barcellos-Hoff MH
通讯作者：
Barcellos-Hoff MH
辐照组织中细胞因子和生长因子表达的长期改变以及与组织学严重程度评分的关系。
影响因子：
3.7
作者：
Gallet P;Phulpin B;Merlin JL;Leroux A;Bravetti P;Mecellem H;Tran N;Dolivet G
通讯作者：
Dolivet G
影响因子：
8.8
作者：
Paquette, B.;Therriault, H.;Desmarais, G.;Wagner, R.;Royer, R.;Bujold, R.
通讯作者：
Bujold, R.
影响因子：
3
作者：
Balin-Gauthier, D;Delord, JP;Allal, C
通讯作者：
Allal, C
影响因子：
4
作者：
MORRIS, VL;KOOP, S;GROOM, AC
通讯作者：
GROOM, AC