The extracellular matrix (ECM) is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D) culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D), physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators) are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning) can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1) biochemical factors modulating breast cancer cell-ECM interactions and (2) 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments.
This study examined the function held by justification of environmentally harmful behavior in the relationship between environmental attitudes and environmental behavior. We tested this function in a cross-cultural context hypothesizing culture-dependent relationship between justification and reported behavior. One-hundred American and 100 Hungarian middle class participants responded to the New Environmental Paradigm scale (NEP), the General Ecological Behavior scale (GEB), and self-developed scales for measuring perceived criticality of environmentally significant behaviors and justification for non-behavior. Environmental attitudes and reported proenvironmental behavior were positively correlated irrespective of culture. However, in case of Americans justification appeared to be an organic element of an array beginning with attitudes and ending at behavior, while Hungarians justified non-behavior independently of pro-environmental activities, influenced only by proenvironmental attitudes. Furthermore we observed higher scores on justification, NEP, and GEB scales among Hungarians. Gender differences appeared only among Americans where women showed more environmental concern than men.
parental wild-type cells. In this study, we identified a novel role for ERK5 in tumor growth kinetics through modulation of the ECM and angiogenesis axis in breast cancer.
As the most abundant source of renewable aromatic compounds on the planet, lignin is an attractive feedstock for producing a range of chemicals and products that are currently derived from petroleum. Despite its great potential, separation of lignin depolymerization products remains one of the main obstacles toward cost-effective lignin valorization. Two lignin-rich streams, residues from enzymatic hydrolysis of the dilute acid and alkaline-pretreated corn stover, were depolymerized via pyrolysis using induction heating and catalytic transfer hydrogenolysis (CTH), respectively. Differences in phenolic compounds from gas chromatography–mass spectrometry and gel permeation chromatography analyses suggest that both pretreatment conditions and lignin depolymerization methods affected the product distribution. CTH lignin oils contain less polar compounds as compared to pyrolysis lignin oils, probably due to saturation of the derived compounds as a result of the reductive chemistry. The resulting liquid oils were subjected to sequential liquid–liquid extraction using a series of solvents with different polarities: hexane, petroleum ether, chloroform, and ethyl acetate. Sequential extraction fractionated lignin-derived oil into groups of different compounds depending on the solvent polarities. This study provides a better understanding of how the lignin source and processing method affect the depolymerization products and provides a possible way to fractionate lignin-derived compounds.
Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.
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