Solid stress inhibits the growth of multicellular tumor spheroids
Solid stress inhibits the growth of multicellular tumor spheroids
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DOI：
10.1038/nbt0897-778
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发表时间：
1997-08-01
影响因子：
46.9
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Helmlinger, G;Netti, PA;Jain, RK
在正常组织中，生长、重塑和形态发生的过程受到应力场的严格调节;相反，应力可能由这些过程产生。我们证明，固体应力抑制体外肿瘤生长，无论宿主物种，组织来源，或分化状态。琼脂糖基质中多细胞肿瘤球体生长的抑制应力为45至120 mm Hg。这种应力大大超过肿瘤血管中的血压，足以在体内诱导肿瘤中血管或淋巴管的塌陷，并且可以解释先前在实体瘤中报道的血流受损、淋巴引流不良和次优药物递送。压力诱导的生长抑制的平台期球体伴随着，在细胞水平上，细胞凋亡减少，增殖没有显着变化。观察到细胞堆积密度的伴随增加，这可能通过细胞体积或细胞形状转导机制阻止细胞发生凋亡。这些结果表明，固体应力在宏观和细胞水平上控制肿瘤生长，从而影响肿瘤进展和治疗剂的递送。
In normal tissues, the processes of growth, remodeling, and morphogenesis are tightly regulated by the stress field; conversely, stress may be generated by these processes. We demonstrate that solid stress inhibits tumor growth iii vitro, regardless of host species, tissue of origin, or differentiation state. The inhibiting stress for multicellular tumor spheroid growth in agarose matrices was 45 to 120 mm Hg. This stress, which greatly exceeds blood pressure in tumor vessels, is sufficient to induce the collapse of vascular or lymphatic vessels in tumors in vivo and can explain impaired blood flow, poor lymphatic drainage, and suboptimal drug delivery previously reported in solid tumors. The stress-induced growth inhibition of plateau-phase spheroids was accompanied, at the cellular level, by decreased apoptosis with no significant changes in proliferation. A concomitant increase In the cellular packing density was observed, which may prevent cells from undergoing apoptosis via a cell-volume or cell-shape transduction mechanism. These results suggest that solid stress controls tumor growth at both the macroscopic and cellular levels, and thus influences tumor progression and delivery of therapeutic agents.