scholarly journals Aberrant Sialylation in Cancer: Biomarker and Potential Target for Therapeutic Intervention?

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2014
Author(s):  
Silvia Pietrobono ◽  
Barbara Stecca
Keyword(s):  
Cancer Progression ◽  
Human Cancer ◽  
Prognostic Significance ◽  
Cancer Treatments ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Anti Cancer ◽  
Altered Gene ◽  
Cell Matrix Interactions ◽  
The Impact

Sialylation is an integral part of cellular function, governing many biological processes including cellular recognition, adhesion, molecular trafficking, signal transduction and endocytosis. Sialylation is controlled by the levels and the activities of sialyltransferases on glycoproteins and lipids. Altered gene expression of these enzymes in cancer yields to cancer-specific alterations of glycoprotein sialylation. Mounting evidence indicate that hypersialylation is closely associated with cancer progression and metastatic spread, and can be of prognostic significance in human cancer. Aberrant sialylation is not only a result of cancer, but also a driver of malignant phenotype, directly impacting key processes such as tumor cell dissociation and invasion, cell-cell and cell-matrix interactions, angiogenesis, resistance to apoptosis, and evasion of immune destruction. In this review we provide insights on the impact of sialylation in tumor progression, and outline the possible application of sialyltransferases as cancer biomarkers. We also summarize the most promising findings on the development of sialyltransferase inhibitors as potential anti-cancer treatments.

scholarly journals Opposite Roles of Tra2β and SRSF9 in the v10 Exon Splicing of CD44

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3195
Author(s):  
Jagyeong Oh ◽  
Yongchao Liu ◽  
Namjeong Choi ◽  
Jiyeon Ha ◽  
Davide Pradella ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Protein Isoforms ◽  
Splicing Regulation ◽  
Transmembrane Glycoprotein ◽  
Cell Matrix ◽  
Exon Splicing ◽  
Matrix Interactions ◽  
Splicing Variants ◽  
Cell Matrix Interactions ◽  
Membrane Region

CD44 is a transmembrane glycoprotein involved in cell–cell and cell–matrix interactions. Several CD44 protein isoforms are generated in human through alternative splicing regulation of nine variable exons encoding for the extracellular juxta-membrane region. While the CD44 splicing variants have been described to be involved in cancer progression and development, the regulatory mechanism(s) underlying their production remain unclear. Here, we identify Tra2β and SRSF9 as proteins with opposite roles in regulating CD44 exon v10 splicing. While Tra2β promotes v10 inclusion, SRSF9 inhibits its inclusion. Mechanistically, we found that both proteins are able to target v10 exon, with GAAGAAG sequence being the binding site for Tra2β and AAGAC that for SRSF9. Collectively, our data add a novel layer of complexity to the sequential series of events involved in the regulation of CD44 splicing.

scholarly journals Nanocellulose-Based Inks for 3D Bioprinting: Key Aspects in Research Development and Challenging Perspectives in Applications—A Mini Review

2020 ◽  
Vol 7 (2) ◽  
pp. 40 ◽  
Author(s):  
Xiaoju Wang ◽  
Qingbo Wang ◽  
Chunlin Xu
Keyword(s):  
Cellulose Nanofibers ◽  
Structural Similarity ◽  
3D Bioprinting ◽  
Mechanical Stiffness ◽  
In Vivo Models ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
The Impact

Nanocelluloses have emerged as a catalogue of renewable nanomaterials for bioink formulation in service of 3D bioprinting, thanks to their structural similarity to extracellular matrices and excellent biocompatibility of supporting crucial cellular activities. From a material scientist’s viewpoint, this mini-review presents the key research aspects of the development of the nanocellulose-based bioinks in 3D (bio)printing. The nanomaterial properties of various types of nanocelluloses, including bacterial nanocellulose, cellulose nanofibers, and cellulose nanocrystals, are reviewed with respect to their origins and preparation methods. Different cross-linking strategies to integrate into multicomponent nanocellulose-based bioinks are discussed in terms of regulating ink fidelity in direct ink writing as well as tuning the mechanical stiffness as a bioactive cue in the printed hydrogel construct. Furthermore, the impact of surface charge and functional groups on nanocellulose surface on the crucial cellular activities (e.g., cell survival, attachment, and proliferation) is discussed with the cell–matrix interactions in focus. Aiming at a sustainable and cost-effective alternative for end-users in biomedical and pharmaceutical fields, challenging aspects such as biodegradability and potential nanotoxicity of nanocelluloses call for more fundamental comprehension of the cell–matrix interactions and further validation in in vivo models.

Exploiting maleimide-functionalized hyaluronan hydrogels to test cellular responses to physical and biochemical stimuli

2021 ◽  
Author(s):  
Andrea Mazzocchi ◽  
Kyung Min Yoo ◽  
Kylie Nairon ◽  
L. Madison Kirk ◽  
Elaheh Rahbar ◽  
...  
Keyword(s):  
3D Models ◽  
Cell Phenotype ◽  
Rgd Peptides ◽  
Encapsulated Cells ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
Cell Phenotypes ◽  
The Impact

Abstract Current in vitro 3D models of liver tissue have been limited by the inability to study the effects of specific extracellular matrix (ECM) components on cell phenotypes. This is in part due to limitations in the availability of chemical modifications appropriate for this purpose. For example, hyaluronic acid (HA), which is a natural ECM component within the liver, lacks key ECM motifs (e.g., RGD peptides) that support cell adhesion. However, the addition of maleimide (Mal) groups to HA could facilitate the conjugation of ECM biomimetic peptides with thiol-containing end groups. In this study, we characterized a new crosslinkable hydrogel (i.e., HA-Mal) that yielded a simplified ECM-mimicking microenvironment supportive of 3D liver cell culture. We then performed a series of experiments to assess the impact of physical and biochemical signaling in the form of RGD peptide incorporation and TGF- ß supplementation, respectively, on hepatic functionality. Hepatic stellate cells (i.e., LX-2) exhibited increased cell-matrix interactions in the form of cell spreading and elongation within HA-Mal matrices containing RGD peptides, enabling physical adhesions, whereas hepatocyte-like cells (HepG2) had reduced albumin and urea production. We further exposed the encapsulated cells to soluble TGF-ß to elicit a fibrosis-like state. In the presence of TGF-ß biochemical signals, LX-2 cells became activated and HepG2 functionality significantly decreased in both RGD-containing and RGD-free hydrogels. Altogether, in this study we have developed a hydrogel biomaterial platform that allows for discrete manipulation of specific ECM motifs within the hydrogel to better understand the roles of cell-matrix interactions on cell phenotype and overall liver functionality.

scholarly journals The inhibition of in vivo tumorigenesis of osteosarcoma (OS)-732 cells by antisense human osteopontin RNA

2008 ◽  
Vol 13 (1) ◽  
Author(s):  
Si-Jin Liu ◽  
Dao-Qiang Zhang ◽  
Xiu-Mei Sui ◽  
Lin Zhang ◽  
Zi-Wei Cai ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Progression ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Model Studies ◽  
Cell Matrix ◽  
Patient Prognosis ◽  
Cell Matrix Interactions

AbstractOsteopontin (OPN) is a secreted, non-collagenous, sialic acid-rich protein which functions by mediating cell-matrix interactions and cellular signaling via binding with integrins and CD44 receptors. An increasing number of studies have shown that OPN plays an important role in controlling cancer progression and metastasis. OPN was found to be expressed in many human cancer types, and in some cases, its over-expression was shown to be directly associated with poor patient prognosis. In vitro cancer cell line and animal model studies have clearly indicated that OPN can function in regulating the cell signaling that ultimately controls the oncogenic potential of various cancers. Previous studies in our laboratory demonstrated that OPN is highly expressed in human osteosarcoma (OS) cell line OS-732. In this study, we successfully reduced the tumorigenecity of OS-732 cells xenotransplanted into nude mice, using the antisense human OPN (hOPN) RNA expression vector.

Use of F9 teratocarcinoma STEM cells to study cell-matrix interactions in the early mouse embryo

1992 ◽  
Vol 50 (1) ◽  
pp. 602-603
Author(s):  
Marc Lenburg ◽  
Rulang Jiang ◽  
Lengya Cheng ◽  
Laura Grabel
Keyword(s):  
Mouse Embryo ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Types ◽  
Embryoid Bodies ◽  
F9 Cells ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions ◽  
F9 Teratocarcinoma

We are interested in defining the cell-cell and cell-matrix interactions that help direct the differentiation of extraembryonic endoderm in the peri-implantation mouse embryo. At the blastocyst stage the mouse embryo consists of an outer layer of trophectoderm surrounding the fluid-filled blastocoel cavity and an eccentrically located inner cell mass. On the free surface of the inner cell mass, facing the blastocoel cavity, a layer of primitive endoderm forms. Primitive endoderm then generates two distinct cell types; parietal endoderm (PE) which migrates along the inner surface of the trophectoderm and secretes large amounts of basement membrane components as well as tissue-type plasminogen activator (tPA), and visceral endoderm (VE), a columnar epithelial layer characterized by tight junctions, microvilli, and the synthesis and secretion of α-fetoprotein. As these events occur after implantation, we have turned to the F9 teratocarcinoma system as an in vitro model for examining the differentiation of these cell types. When F9 cells are treated in monolayer with retinoic acid plus cyclic-AMP, they differentiate into PE. In contrast, when F9 cells are treated in suspension with retinoic acid, they form embryoid bodies (EBs) which consist of an outer layer of VE and an inner core of undifferentiated stem cells. In addition, we have established that when VE containing embryoid bodies are plated on a fibronectin coated substrate, PE migrates onto the matrix and this interaction is inhibited by RGDS as well as antibodies directed against the β1 integrin subunit. This transition is accompanied by a significant increase in the level of tPA in the PE cells. Thus, the outgrowth system provides a spatially appropriate model for studying the differentiation and migration of PE from a VE precursor.

Cell matrix interactions in asthma

1997 ◽  
Vol 27 (1) ◽  
pp. 22-27
Author(s):  
K. GOLDRING ◽  
J. A. WARNER
Keyword(s):  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions

scholarly journals A computational framework for modeling cell–matrix interactions in soft biological tissues

2021 ◽  
Author(s):  
Jonas F. Eichinger ◽  
Maximilian J. Grill ◽  
Iman Davoodi Kermani ◽  
Roland C. Aydin ◽  
Wolfgang A. Wall ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Three Dimensional ◽  
Biological Tissues ◽  
Computational Framework ◽  
Cell Matrix ◽  
Physiological Processes ◽  
Matrix Interactions ◽  
Mechanical Homeostasis ◽  
Cell Matrix Interactions ◽  
Short Time

AbstractLiving soft tissues appear to promote the development and maintenance of a preferred mechanical state within a defined tolerance around a so-called set point. This phenomenon is often referred to as mechanical homeostasis. In contradiction to the prominent role of mechanical homeostasis in various (patho)physiological processes, its underlying micromechanical mechanisms acting on the level of individual cells and fibers remain poorly understood, especially how these mechanisms on the microscale lead to what we macroscopically call mechanical homeostasis. Here, we present a novel computational framework based on the finite element method that is constructed bottom up, that is, it models key mechanobiological mechanisms such as actin cytoskeleton contraction and molecular clutch behavior of individual cells interacting with a reconstructed three-dimensional extracellular fiber matrix. The framework reproduces many experimental observations regarding mechanical homeostasis on short time scales (hours), in which the deposition and degradation of extracellular matrix can largely be neglected. This model can serve as a systematic tool for future in silico studies of the origin of the numerous still unexplained experimental observations about mechanical homeostasis.

Osteoblast-derived acetylcholinesterase: a novel mediator of cell-matrix interactions in bone?

Bone ◽  
1999 ◽  
Vol 24 (4) ◽  
pp. 297-303 ◽  
Author(s):  
P.G Genever ◽  
M.A Birch ◽  
E Brown ◽  
T.M Skerry
Keyword(s):  
Cell Matrix ◽  
Matrix Interactions ◽  
Cell Matrix Interactions
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