Molecular weight of surface immobilized hyaluronic acid influences CD44-mediated binding of gastric cancer cells.
Molecular weight of surface immobilized hyaluronic acid influences CD44-mediated binding of gastric cancer cells.
复制标题
DOI：
10.1038/s41598-018-34445-0
复制
发表时间：
2018-10-30
影响因子：
4.6
通讯作者：
Pires RA
中科院分区：
文献类型：
--
作者：
Amorim S;da Costa DS;Freitas D;Reis CA;Reis RL;Pashkuleva I;Pires RA
透明质酸（HA）与其主要膜受体CD 44之间的相互作用在病理过程（例如癌症）中的生理重要性已被充分认识。然而，这些相互作用主要是在溶液中研究，而HA在细胞外基质（ECM）是部分固定通过其与其他ECM成分的相互作用。因此，我们开发了HA以ECM相关方式呈现的基质。我们以逐层（LbL）方式固定了不同分子量（Mw）的HA，并研究了底物与CD44和两种过表达该受体的人胃癌细胞系（即AGS和MKN 45）的相互作用。我们证明，MKN 45细胞是更敏感的LbL底物相比，AGS。这种差异是由于不同的CD44表达：虽然CD44主要在AGS的细胞质中检测到，但MKN 45主要在细胞膜上表达CD44，在细胞膜上参与HA的识别和结合。研究的细胞系的侵袭性也作为HA Mw的函数进行评价。当MKN 45细胞与呈现高分子量HA的基质接触时，观察到侵袭性特征，其特征在于低细胞粘附、高细胞运动性、高皮质素表达、侵袭伪足和细胞簇的形成。
The physiological importance of the interactions between hyaluronic acid (HA) and its main membrane receptor, CD44, in pathological processes, e.g. cancer, is well recognized. However, these interactions are mainly studied in solution, whereas HA in the extracellular matrix (ECM) is partially immobilized via its interactions with other ECM components. We therefore, developed substrates in which HA is presented in an ECM-relevant manner. We immobilized HA with different molecular weights (Mw) in a Layer-by-Layer (LbL) fashion and studied the interactions of the substrates with CD44 and two human gastric cancer cell lines that overexpress this receptor, namely AGS and MKN45. We demonstrate that MKN45 cells are more sensitive to the LbL substrates as compared with AGS. This difference is due to different CD44 expression: while CD44 is detected mainly in the cytoplasm of AGS, MKN45 express CD44 predominantly at the cell membrane where it is involved in the recognition and binding of HA. The invasiveness of the studied cell lines was also evaluated as a function of HA Mw. Invasive profile characterized by low cell adhesion, high cell motility, high expression of cortactin, formation of invadopodia and cell clusters was observed for MKN45 cells when they are in contact with substrates presenting HA of high Mw.
登录
查看更多内容
DOI：
10.1073/pnas.95.21.12271
发表时间：
1998-10-13
影响因子：
11.1
作者：
Höök, F;Rodahl, M;Brzezinski, P
通讯作者：
Brzezinski, P
DOI：
10.1016/s1357-2725(01)00166-2
发表时间：
2002-07-01
影响因子：
4
作者：
Isacke, CM;Yarwood, H
通讯作者：
Yarwood, H
影响因子：
3.9
作者：
Amorim, Sara;Pires, Ricardo A.;Pashkuleva, Iva
通讯作者：
Pashkuleva, Iva
影响因子：
3.2
作者：
Chen, Jee-Wei E.;Pedron, Sara;Harley, Brendan A. C.
通讯作者：
Harley, Brendan A. C.
影响因子：
7.8
作者：
Helwani, FM;Kovacs, EM;Yap, AS
通讯作者：
Yap, AS