3B's Research Group, Research Institute on Biomaterials, Biodegradables and Biomimetics (I3Bs), University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, 4805-017, Portugal.
Adv Biosyst. 2020 Nov;4(11):e2000122. doi: 10.1002/adbi.202000122. Epub 2020 Oct 5.
The overproduction and deposition of hyaluronic acid (HA) of different sizes in the tumor microenvironment is associated with cancer metastasis. Here, the development of layer-by-layer (LbL) constructs containing HA of different molecular weights (i.e., 5.6, 618, and 1450 kDa) that mimic the HA-rich cancer extracellular matrix is described to study the effect of the HA's size on the behavior of gastric cancer cells (AGS). The results demonstrate that LbL constructs with short HA, i.e., 5.6 kDa, activate the cytoskeleton rearrangement leading to the "hummingbird" morphology, promote high cellular motility, and activate signaling pathways with increased expression of p-ERK1/2 and p-AKT. In addition, it is demonstrated that this malignant transformation involves an active participation of the HA coreceptor RHAMM in AGS cells.
透明质酸（HA）在肿瘤微环境中的过度产生和沉积与癌症转移有关。在这里，描述了包含不同分子量（即 5.6、618 和 1450 kDa）HA 的层层（LbL）构建体的开发，这些构建体模拟富含 HA 的癌症细胞外基质，以研究 HA 大小对胃癌细胞（AGS）行为的影响。结果表明，具有短 HA（即 5.6 kDa）的 LbL 构建体激活细胞骨架重排导致“蜂鸟”形态，促进高细胞迁移，并通过增加 p-ERK1/2 和 p-AKT 的表达来激活信号通路。此外，还证明这种恶性转化涉及 AGS 细胞中 HA 核心受体 RHAMM 的积极参与。
