Lee Meng-Horng, Wu Pei-Hsun, Gilkes Daniele, Aifuwa Ivie, Wirtz Denis
Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Oncotarget. 2015 Oct 20;6(32):32634-45. doi: 10.18632/oncotarget.4728.
Recent work suggests that the dissemination of tumor cells may occur in parallel with, and even preceed, tumor growth. The mechanism for this early invasion is largely unknown. Here, we find that mammary epithelial cells (MECs) induce neighboring breast carcinoma cells (BCCs) to cross the basement membrane by secreting soluble laminin. Laminin continuously produced by MECs induce long membrane cellular protrusions in BCCs that promote their contractility and invasion into the surrounding matrix. These protrusions depend on microtubule bundles assembled de novo through laminin-integrin β1 signaling. These results describe how non-cancerous MECs can actively participate in the invasive process of BCCs.
近期研究表明,肿瘤细胞的播散可能与肿瘤生长同时发生,甚至早于肿瘤生长。这种早期侵袭的机制在很大程度上尚不清楚。在此,我们发现乳腺上皮细胞(MECs)通过分泌可溶性层粘连蛋白诱导邻近的乳腺癌细胞(BCCs)穿过基底膜。MECs持续产生的层粘连蛋白在BCCs中诱导出长的膜性细胞突起,促进其收缩性并侵入周围基质。这些突起依赖于通过层粘连蛋白-整合素β1信号从头组装的微管束。这些结果描述了非癌细胞MECs如何能够积极参与BCCs的侵袭过程。