Abstract
BackgroundThe extracellular matrix (ECM) is a mosaic of various structural and functional proteins that cooperate with the cell, regulate adhesion, and consequently manage its further fate. Liver destruction is accompanied by a disruption of the physicochemical properties of the ECM which deregulates the cell–ECM interaction and can lead to uncontrolled proliferation and neoplastic transformation of cells. Therefore, it can be assumed that ECM modification and restoration of its characteristics for healthy tissue may counteract uncontrolled cell proliferation. The purpose of the presented research model was to optimise the physical characteristics of ECM by introducing a graphene oxide plane/nanofilm (nfGO) and enriching the cell environment with potentially missing proteins by adding a functional protein cocktail (chicken embryo liver extract) and determine the impact of these factors on cell–ECM cooperation and its consequences on adhesion, proliferation, and cell phase, which are factors of the invasiveness of cancer cells.ResultsExperiments were performed with non-cancer HS-5 cells and liver cancer cells HepG2 and C3A. The cells were divided into four groups: (1) control, (2) cultured on nfGO, (3) cultured with the addition of chicken embryo liver extract (CELE) and (4) cultured on the nfGO with the addition of CELE. CELE contained 1735 proteins; the top 57 of these proteins have been presented. The use of nfGO as well as CELE and nfGO + CELE reduced the proliferation of HepG2 cancer cells to the greatest extent; this is in contrast to non-cancer cells and also to C3A cancer cells. Furthermore, the combined use of the CELE protein cocktail and GO substrate effectively resulted in a decrease in the population of HepG2 cells in the G0/G1 phase and an increase of the population in G2/M. Molecular analysis of HepG2 cancer cells also showed an increase in the expression of genes responsible for adhesion such as focal adhesion kinase (fak), e-cadherin, and n-cadherin and a decrease in β-catenin, which is considered a proto-oncogene.ConclusionsStudies have shown that both the GO surface structure on which the cells are grown as well as the presence of a multi-component natural cocktail of regulatory proteins, can modify the expression of integrins, increase adhesion and, as a consequence, proliferation and the cell cycle—entering the resting phase. For the first time, it has been documented that hepatic cancer cells of the HepG2 line under the influence of stimuli derived from mimic ECM (graphene oxide) in interaction with a unique protein complex derived from chicken liver embryo decreased of the invasiveness of cancer cells.
Highlights
The extracellular matrix (ECM) is a mosaic of various structural and functional proteins that cooperate with the cell, regulate adhesion, and manage its further fate
Sosnowska et al Cancer Nano (2021) 12:2 first time, it has been documented that hepatic cancer cells of the HepG2 line under the influence of stimuli derived from mimic ECM in interaction with a unique protein complex derived from chicken liver embryo decreased of the invasiveness of cancer cells
Chemical groups present on graphene oxide (GO) were identified by the Fourier transform infrared (FTIR) method (Fig. 1b)
Summary
The extracellular matrix (ECM) is a mosaic of various structural and functional proteins that cooperate with the cell, regulate adhesion, and manage its further fate. In the inflammatory process, tumour-associated cells possess impaired secretion of matrix proteins, which leads to overproduction and reorganisation of ECM components. ECM degradation can lead to cancer cell transformation, and the resulting cancer cells stimulate the ECM reorganisation (stiffening) process creating a kind of feedback (Iwasaki et al 2016). Inhibiting this feedback is the key to stopping and possibly treating cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
