Isolation and Molecular Characterization of Circulating Melanoma Cells
Isolation and Molecular Characterization of Circulating Melanoma Cells
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DOI：
10.1016/j.celrep.2014.03.039
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发表时间：
2014-05-01
期刊：
影响因子：
8.8
通讯作者：
Haber, Daniel A.
中科院分区：
文献类型：
--
作者：
Luo, Xi;Mitra, Devarati;Haber, Daniel A.
黑色素瘤是一种侵袭性恶性肿瘤，具有高频率的血源性转移，但循环肿瘤细胞（CTC）尚未容易分离。我们将微流体CTC捕获适应于他莫昔芬驱动的B-RAF/PTEN小鼠黑色素瘤模型。在所有荷瘤小鼠中检测到CTC，并且在B-RAF抑制剂治疗后迅速下降。CTC从局部肿瘤中早期脱落，手术切除后的短期B-RAF抑制足以显著抑制远处转移。荷黑色素瘤小鼠中大量的CTC使得能够将RNA测序谱与匹配的原发性肿瘤进行比较。小鼠黑色素瘤CTC衍生的特征与人黑色素瘤的侵袭性和细胞运动性相关。在转移性黑色素瘤患者中检测到的CTC数量较少，并且随着成功的B-RAF靶向治疗而下降。总之，CTC的捕获和分子表征提供了对黑色素瘤的血行性扩散的深入了解。
Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs) have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.