To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

BackgroundFor metabolic engineering, many rate-limiting steps may exist in the pathways of accumulating the target metabolites. Increasing copy number of the desired genes in these pathways is a general method to solve the problem, for example, the employment of the multi-copy plasmid-based expression system. However, this method may bring genetic instability, structural instability and metabolic burden to the host, while integrating of the desired gene into the chromosome may cause inadequate transcription or expression. In this study, we developed a strategy for obtaining gene overexpression by engineering promoter clusters consisted of multiple core-tac-promoters (MCPtacs) in tandem.ResultsThrough a uniquely designed in vitro assembling process, a series of promoter clusters were constructed. The transcription strength of these promoter clusters showed a stepwise enhancement with the increase of tandem repeats number until it reached the critical value of five. Application of the MCPtacs promoter clusters in polyhydroxybutyrate (PHB) production proved that it was efficient. Integration of the phaCAB genes with the 5CPtacs promoter cluster resulted in an engineered E.coli that can accumulate 23.7% PHB of the cell dry weight in batch cultivation.ConclusionsThe transcription strength of the MCPtacs promoter cluster can be greatly improved by increasing the tandem repeats number of the core-tac-promoter. By integrating the desired gene together with the MCPtacs promoter cluster into the chromosome of E. coli, we can achieve high and stale overexpression with only a small size. This strategy has an application potential in many fields and can be extended to other bacteria.

Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional FeO-Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.

Hydrodynamic shear force plays an important role in the leukocyte adhesion cascade that involves the tethering and rolling of cells along the endothelial layer, their firm adhesion or arrest, and their extravasation or escape from the circulatory system by inducing passive deformation, or cell flattening, and microvilli stretching, as well as regulating the expression, distribution, and conformation of adhesion molecules on leukocytes and the endothelial layer. Similarly, the dissemination of circulating tumor cells (CTCs) from the primary tumor sites is believed to involve tethering, rolling, and firm adhesion steps before their eventual extravasation which leads to secondary tumor sites (metastasis). Of particular importance to both the leukocyte adhesion cascade and the extravasation of CTCs, glycoproteins are involved in all three steps (capture, rolling, and firm adhesion) and consist of a variety of important selectin ligands. This review article provides an overview of glycoprotein glycosylation associated with the abnormal glycan expression on cancer cell surfaces, where well-established and novel selectin ligands that are cancer related are discussed. An overview of computational approaches on the effects of fluid mechanical force on glycoprotein mediated cancer cell rolling and adhesion is presented with a highlight of recent flow-based and selectin-mediated cell capturing/enriching devices. Finally, as an important branch of the glycoprotein family, mucins, specifically MUC1, are discussed in the context of their aberrant expression on cancer cells and their role as cancer cell adhesion molecules. Since metastasis relies heavily on glycoprotein interactions in the bloodstream where the fluid shear stress highly regulates cell adhesion forces, it is important to study and understand the glycomechanics of all relevant glycoproteins (well-established and novel) as they relate to the metastatic cascade.