Immobilized Transforming Growth Factor-Beta 1 in a Stiffness-Tunable Artificial Extracellular Matrix Enhances Mechanotransduction in the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma
| Autor: | Rui-Zhi Tang, Sai-Sai Gu, Kaiping Wang, Xi-Qiu Liu, Xin-Ting Chen, Li-Jie He |
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| Rok vydání: | 2019 |
| Předmět: |
Carcinoma
Hepatocellular Epithelial-Mesenchymal Transition Materials science Matrix (biology) Transforming Growth Factor beta1 Extracellular matrix Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Humans General Materials Science Epithelial–mesenchymal transition Mechanotransduction Cell adhesion 030304 developmental biology 0303 health sciences biology Liver Neoplasms Hep G2 Cells Transforming growth factor beta Vinculin Extracellular Matrix Neoplasm Proteins Cell biology 030220 oncology & carcinogenesis biology.protein Signal transduction Signal Transduction |
| Zdroj: | ACS Applied Materials & Interfaces. 11:14660-14671 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.9b03572 |
| Popis: | Cancer progression is regulated by multiple factors of extracellular matrix (ECM). Understanding how cancer cells integrate multiple signaling pathways to achieve specific behaviors remains a challenge because of the lack of appropriate models to copresent and modulate ECM properties. Here we proposed a strategy to build a thin biomaterial matrix by poly(l-lysine) and hyaluronan as an artificial stiffness-tunable ECM. Transforming growth factor-beta 1 (TGF-β1) was used as a biochemical cue to present in an immobilized and spatially controlled manner, with a high loading efficiency of 90%. Either soft matrix with immobilized TGF-β1 (i-TGF) or bare stiff matrix could only promote HCC cells to form the epithelial phenotype, whereas stiff matrix with i-TGF was the only condition to induce the mesenchymal phenotype. Further investigation revealed that i-TGF increased the specific TGF-β1 receptor (TβRI) expression to activate PI3K pathway. i-TGF-TβRI interactions also promoted HCC cell adhesion to enlarge contact area for stiffness sensing, resulting in the raising expression of the mechano-sensor (β1 integrin). Mechanotransduction would then be enhanced by the β1 integrin/vinculin/p-FAK pathway, leading to a noble PI3K activation. Using our model, a novel mechanism was discovered to elucidate regulation of cell fates by coupling mechanotransduction and biochemical signaling. |
| Databáze: | OpenAIRE |
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