Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
Keratin-14 (KRT14) Positive Leader Cells Mediate Mesothelial Clearance and Invasion by Ovarian Cancer Cells
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DOI：
10.3390/cancers11091228
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发表时间：
2019-09-01
期刊：
影响因子：
5.2
通讯作者：
Stephens, Andrew N.
中科院分区：
文献类型：
--
作者：
Bilandzic, Maree;Rainczuk, Adam;Stephens, Andrew N.
上皮性卵巢癌转移是由球状体驱动的，球状体是从原发性肿瘤块释放的异质性癌细胞聚集体，其被动地散布在整个腹膜腔中以促进肿瘤扩散、疾病复发和获得性化疗耐药性。尽管它们的临床重要性，控制球状体附着和入侵到下面的健康组织的分子事件仍然知之甚少。我们研究了一种新的体外侵袭模型，使用成像质谱建立一个"快照"的球体/mesotherapy接口。在众多的粘附相关蛋白，我们确定了一个亚群的高度能动性，侵袭性细胞表达的基底上皮标志物KRT 14作为一个绝对的决定因素的侵袭潜力。KRT14的缺失完全消除了侵袭能力，但对细胞活力或增殖没有影响，表明了侵袭特异性作用。我们的数据表明KRT14细胞作为卵巢癌"领导细胞"表型的肿瘤侵袭，并建议其作为临床相关的目标，在定向抗肿瘤治疗的重要性。
Epithelial ovarian cancer metastasis is driven by spheroids, which are heterogeneous cancer cell aggregates released from the primary tumour mass that passively disseminate throughout the peritoneal cavity to promote tumour spread, disease recurrence, and acquired chemoresistance. Despite their clinical importance, the molecular events that control spheroid attachment and invasion into underlying healthy tissues remain poorly understood. We examined a novel in vitro invasion model using imaging mass spectrometry to establish a "snapshot" of the spheroid/mesothelial interface. Amongst numerous adhesion-related proteins, we identified a sub-population of highly motile, invasive cells that expressed the basal epithelial marker KRT14 as an absolute determinant of invasive potential. The loss of KRT14 completely abrogated the invasive capacity, but had no impact on cell viability or proliferation, suggesting an invasion-specific role. Our data demonstrate KRT14 cells as an ovarian cancer "leader cell" phenotype underlying tumor invasion, and suggest their importance as a clinically relevant target in directed anti-tumour therapies.