RESUMO
Cancer cell progression and proliferation increase cell density, resulting in changes to the tumour site, including the microenvironment. What is not known is if increased cell density influences the aggressiveness of cancer cells, especially their proliferation, migration, and invasion capabilities. In this study, we found that dense cell culture enhances the aggressiveness of the metastatic cancer cell lines, 4T1 and ZR-75-30, by increasing their proliferation, migration, and invasion capabilities. However, a less metastatic cell line, MCF-7, did not show an increase in aggressiveness, following dense cell culture conditions. We conducted a differential proteomic analysis on 4T1 cells cultured under dense or sparse conditions and identified an increase in expression for proteins involved in migration, including focal adhesion, cytoskeletal reorganization, and transendothelial migration. In contrast, 4T1 cells grown under sparse conditions had higher expression levels for proteins involved in metabolism, including lipid and phospholipid binding, lipid and cholesterol transporter activity, and protein binding. These results suggest that the high-density tumour microenvironment can cause a change in cellular behaviour, leading towards more aggressive cancers. SIGNIFICANCE OF THE STUDY: Metastasis of cancer cells is an obstacle to the clinical treatment of cancer. We found that dense cultures made metastatic cancer cells more potent in terms of proliferation, migration, and invasion. The proteomic and bioinformatic analyses provided some valuable clues for further intensive studies about the effects of cell density on cancer cell aggressiveness, which were associated with events such as pre-mRNA splicing and RNA transport, focal adhesion and cytoskeleton reorganization, ribosome biogenesis, and transendothelial migration, or associated with proteins, such as JAM-1 and S100A11. This investigation gives us new perspectives to investigate the metastasis mechanisms related to the microenvironment of tumour sites.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias Mamárias Animais/metabolismo , Proteínas de Neoplasias/metabolismo , Proteômica , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/genéticaRESUMO
The geometrical structures, electrical properties, and nonlinear optical (NLO) properties of AlNNT-Li and BNNT-Li nanotube systems were investigated by means of the density functional theory (DFT) method. Frontier molecular orbitals and density of states analyses show that adsorption of the Li atom can significantly narrow the wide HOMO-LUMO gaps of pure AlNNT and BNNT. The results reveal that AlNNT-Li and BNNT-Li systems containing diffuse excess electrons can be regarded as inorganic electrides. The formation of diffuse excess electrons leads to a decrease in transition energies, thereby increasing the first hyperpolarizabilities (ß 0) of AlNNT-Li and BNNT-Li. This work may contribute to the development of potential high-performance NLO materials. Graphical abstract The structural characteristics and nonlinear optical properties of the AlNNT-Li and BNNT-Li systems were studied by means of density functional theory. Introduction of Li atoms greatly enhances the static first hyperpolarizabilities of AlNNT-Li and BNNT-Li.