Rigid tumours contain soft cancer cells
Rigid tumours contain soft cancer cells
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硬肿瘤含有软癌细胞
DOI：
10.1038/s41567-022-01755-0
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发表时间：
2022-09-29
期刊：
影响因子：
19.6
通讯作者：
Kaes, Josef A.
中科院分区：
文献类型：
--
作者：
Fuhs, Thomas;Wetzel, Franziska;Kaes, Josef A.
触诊利用了实体乳腺肿瘤比周围组织更硬的事实。然而，癌细胞往往会软化，这可能会增强它们挤压致密组织的能力。这种明显的悖论提出了两个相互矛盾的假设：要么柔软性是由于适应肿瘤微环境而产生的，要么软性癌细胞已经存在于坚硬的原发性肿瘤块内，从而引起癌细胞运动。我们在多个长度尺度上研究来自乳腺癌和宫颈癌患者的原发性肿瘤外植体。我们发现原发性肿瘤的机械特性在从组织水平到单个细胞的所有尺度上都具有高度异质性。这导致了广泛的刚性分布——从非常僵硬的细胞到比健康组织中发现的更软的细胞——转向更高比例的较软细胞。基于原子力显微镜的组织流变学表明，刚性细胞岛被软细胞包围。对生命细胞的追踪证实了肿瘤外植体中堵塞区域和未堵塞区域的共存。尽管不存在僵硬细胞的渗透骨架和大部分未堵塞的活动细胞，但癌细胞簇表现出异质固体行为，其有限的弹性模量提供了机械稳定性。子宫颈癌和乳腺癌在不同尺度上的机械特性具有高度异质性。这种异质性为肿瘤提供了稳定性和细胞运动的空间。
Palpation utilizes the fact that solid breast tumours are stiffer than the surrounding tissue. However, cancer cells tend to soften, which may enhance their ability to squeeze through dense tissue. This apparent paradox proposes two contradicting hypotheses: either softness emerges from adaptation to the tumour's microenvironment or soft cancer cells are already present inside a rigid primary tumour mass giving rise to cancer cell motility. We investigate primary tumour explants from patients with breast and cervix carcinomas on multiple length scales. We find that primary tumours are highly heterogeneous in their mechanical properties on all scales from the tissue level down to individual cells. This results in a broad rigidity distribution-from very stiff cells to cells softer than those found in healthy tissue-that is shifted towards a higher fraction of softer cells. Atomic-force-microscopy-based tissue rheology reveals that islands of rigid cells are surrounded by soft cells. The tracking of vital cells confirms the coexistence of jammed and unjammed areas in tumour explants. Despite the absence of a percolated backbone of stiff cells and a large fraction of unjammed, motile cells, cancer cell clusters show a heterogeneous solid behaviour with a finite elastic modulus providing mechanical stability.Cervix and breast carcinomas are highly heterogeneous in their mechanical properties across scales. This heterogeneity provides the tumour with stability and room for cell motility.