Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.
Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.
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DOI：
10.1371/journal.pone.0058859
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Parent CA
中科院分区：
文献类型：
--
作者：
Weiger MC;Vedham V;Stuelten CH;Shou K;Herrera M;Sato M;Losert W;Parent CA
癌细胞在肿瘤进展过程中改变其迁移特性，侵入周围组织并转移到远处。然而，目前尚不清楚不同恶性肿瘤细胞之间的迁移行为有何不同，以及这些迁移行为是否可以用来评估肿瘤细胞的恶性潜能。在这里，我们分析了代表乳腺癌进展不同阶段的细胞系的迁移行为，使用常规迁移测定或延时成像和粒子图像速度测定（PIV）来捕捉迁移动力学。我们发现，在transwell实验中迁移细胞的数量，以及在无约束的二维实验中迁移的距离和速度，与恶性潜能没有相关性。然而，在二维迁移过程中，细胞运动的方向性很好地区分了良性和致瘤细胞系，致瘤细胞系的定向运动较少，更随机。此外，在基础条件下观察到的上皮片的迁移行为和对表皮生长因子（EGF）或溶血磷酸酸（LPA）刺激的反应在细胞速度、方向性和时空运动模式方面对每个细胞系都是不同的。令人惊讶的是，与基础条件或EGF刺激相比，LPA治疗可促进肺集落形成的MCF10CA1a细胞更有凝聚力、更有方向性的片状运动，这意味着LPA信号通路可能改变MCF10CA1a细胞的侵袭潜能。总之，我们的研究结果确定了细胞方向性是评估乳腺癌细胞系致瘤潜力的一个有希望的指标，并表明LPA在转移性乳腺癌细胞亚群中诱导了更多的内聚运动。
Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV) to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF) or lysophosphatitic acid (LPA) are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.
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影响因子：
8
作者：
Harma, V.;Knuuttila, M.;Virtanen, J.;Mirtti, T.;Kohonen, P.;Kovanen, P.;Happonen, A.;Kaewphan, S.;Ahonen, I.;Kallioniemi, O.;Grafstrom, R.;Lotjonen, J.;Nees, M.
通讯作者：
Nees, M.
影响因子：
3.7
作者：
Kadota M;Yang HH;Gomez B;Sato M;Clifford RJ;Meerzaman D;Dunn BK;Wakefield LM;Lee MP
通讯作者：
Lee MP
影响因子：
50.5
作者：
Ferrero, JM;Ramaioli, A;Milano, G
通讯作者：
Milano, G
影响因子：
4.3
作者：
Garcia, Ruben;Franklin, Richard A.;McCubrey, James A.
通讯作者：
McCubrey, James A.
影响因子：
4
作者：
Joslin, Elizabeth J.;Opresko, Lee K.;Lauffenburger, Douglas A.
通讯作者：
Lauffenburger, Douglas A.