Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells

Background: Glioblastoma (GBM), the most malignant primary brain tumor, leads to poor and unpredictable clinical outcomes. Recent studies showed the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. In this context, we investigated how GBM cells modulate resident glial cells, particularly their paracrine activity, and how this modulation can influence back on the malignant phenotype of GBM cells. Methods: Conditioned media (CM) of primary mouse glial cultures unexposed (unprimed) or exposed (primed) to the secretome of GL261 GBM cells were analyzed by proteomic analysis. Additionally, these CM were used in GBM cells to evaluate their impact in glioma cell viability, migration capacity and activation of tumor-related intracellular pathways. Results: The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells. At the functional levels, CM derived from unprimed glial cells favored an increase in GBM cell migration capacity, while CM from primed glial cells promoted cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. Conclusions: Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the "go-or-grow" phenotypic switch of GBM cells.Fundação para a Ciência e Tecnologia (IF/00601/2012 to B.M.C.; IF/00111 to A.J.S; SFRH/BD/52287/2013 to A.I.O.; SFRH/BD/81495/2011 to S.I.A.; SFRH/BD/88121/2012 to J.V.C.; projects PTDC/SAU-GMG/113795/2009 to B.M.C.; PTDC/NEU-NMC/0205/2012, PTDC/NEU-SCC/7051/2014, PEst-C/SAU/LA0001/2013–2014 and UID/NEU/04539/2013 to B.M.), Liga Portuguesa Contra o Cancro (B.M.C.), Fundação Calouste Gulbenkian (B.M.C.) and Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC; to A.I.O.). Project co-financed by Programa Operacional Regional do Norte (ON.2—O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER), Programa Operacional Factores de Competitividade (COMPETE), and by The National Mass Spectrometry Network (RNEM) under the contract REDE/1506/REM/2005info:eu-repo/semantics/publishedVersio

The Committee on Economic Education: Its Effect on the Introductory Course and Women in Economics

CEE, CSWEP, Diversity, Economics majors, Teaching, Women,

Biomaterials developments for brain tissue engineering

The Central Nervous System (CNS) is a highly complex organ that works as the control centre of the body, managing vital and non-vital functions. Neuro-diseases can lead to the degeneration of neural tissue, breakage of the neuronal networks which can affect vital functions and originate cognitive deficits. The complexity of the neural networks, their components and the low regenerative capacity of the CNS are on the basis for the lack of recovery, having the need for therapies that can promote tissue repair and recovery. Most brain processes are mediated through molecules (e.g. cytokines, neurotransmitters) and cells response accordingly and to surrounding cues, either biological or physical, which offers molecule administration and/or cell transplantation a great potential for use in brain recovery. Biomaterials and in particular, of natural origin are attractive candidates owed to their intrinsic biological cues and biocompatibility and degradability. Through the use of biomaterials, it is possible to protect the cells/molecules from body clearance, enzymatic degradation while maintaining the components in a place of interest. Moreover, by means of combining several components, it is possible to obtain a more targeted and controlled delivery, to image the biomaterial implantation and its degradation over time and tackling simultaneously occurring events (cell death and inflammation) in brain diseases. In this chapter, it is reviewed some brain-affecting diseases and the current developments on tissue engineering approaches for a functional recovery of the brain from those diseases.(undefined)info:eu-repo/semantics/publishedVersio

4D printing and stimuli-responsive materials in biomedical aspects

Three-dimensional (3D) printing has revolutionized the world manufacturing production. In biomedical applications, however, 3D printed constructs fell short of expectations mainly due to their inability to adequately mimic the dynamic human tissues. To date, most of the 3D printed biomedical structures are largely static and inanimate as they lack the time-dependant dimension. To adequately address the dynamic healing and regeneration process of human tissues, 4D printing emerges as an important development where "time" is incorporated into the conventional concept of 3D printing as the fourth dimension. As such, additive manufacturing (AM) evolves from 3D to 4D printing and in the process putting stimulus-responsive materials in the limelight. In this review, the state-of-the-art efforts in integrating the time-dependent behaviour of stimulus-responsive materials in 4D printing will be discussed. In addition, current literatures on the interactions between various types of stimuli (categorized under physical, chemical and biological signals) with the associated stimulus-responsive materials will be the major focus in this review. Lastly, potential usage of 4D printing in biomedical applications will also be discussed, followed by technical considerations as well as outlook for future discoveries. STATEMENT OF SIGNIFICANCE: In this Review, we have demonstrated the significance of 4D printing in biomedical applications, in which "time" has been incorporated into the conventional concept of 3D printing as the 4th dimension. As such, 4D printing differentiates and evolves from 3D printing using stimulus-responsive materials which can actively respond to external stimuli and more sophisticated "hardware"-printer which can achieve multi-printing via mathematical-predicted designs that are programmed to consider the transformation of 3D constructs over time. The emphasize will be on the interactions between various types of stimuli (categorized under physical, chemical and biological signals) with the associated stimulus-responsive materials, followed by technical considerations as well as outlook for future discoveries.Accepted versio