Extracellular matrix biomechanical roles and adaptation in health and disease.

Extracellular matrices (ECMs) are dynamic 3D macromolecular networks that exhibit structural characteristics and composition specific to different tissues, serving various biomechanical and regulatory functions. The interactions between ECM macromolecules such as collagen, elastin, glycosaminoglycans (GAGs), proteoglycans (PGs), fibronectin, and laminin, along with matrix effectors and water, contribute to the unique cellular and tissue functional properties during organ development, tissue homoeostasis, remodeling, disease development, and progression. Cells adapt to environmental changes by adjusting the composition and array of ECM components.

Colorectal Cancer Cell Invasion and Functional Properties Depend on Peri-Tumoral Extracellular Matrix.

We investigated how the extracellular matrix (ECM) affects LoVo colorectal cancer cells behavior during a spatiotemporal invasion. Epithelial-to-mesenchymal transition (EMT) markers, matrix-degrading enzymes, and morphological phenotypes expressed by LoVo-S (doxorubicin-sensitive) and higher aggressive LoVo-R (doxorubicin-resistant) were evaluated in cells cultured for 3 and 24 h on Millipore filters covered by Matrigel, mimicking the basement membrane, or type I Collagen reproducing a desmoplastic lamina propria. EMT and invasiveness were investigated with RT-qPCR, Western blot, and scanning electron microscopy.

Studying the Effects of Glycosaminoglycans in Cell Morphological Aspect with Scanning Electron Microscopy.

Glycosaminoglycans, the building blocks of proteoglycans, play a central role in the extracellular matrix and regulate a number of cellular processes. Therefore, any imbalance in their levels can lead to significant changes in cell behavior and phenotype. Additionally, glycosaminoglycans and their derivatives can be deployed as therapeutic agents in pathological conditions.

Substrate Type and Concentration Differently Affect Colon Cancer Cells Ultrastructural Morphology, EMT Markers, and Matrix Degrading Enzymes.

Aim of the study was to understand the behavior of colon cancer LoVo-R cells (doxorubicin-resistant) vs. LoVo-S (doxorubicin sensitive) in the initial steps of extracellular matrix (ECM) invasion. We investigated how the matrix substrates Matrigel and type I collagen-mimicking the basement membrane (BM) and the normal or desmoplastic lamina propria, respectively-could affect the expression of epithelial-to-mesenchymal transition (EMT) markers, matrix-degrading enzymes, and phenotypes.

Heparanase regulates EMT and cancer stem cell properties in prostate tumors.

Prostate cancer displays a certain phenotypic plasticity that allows for the transition of cells from the epithelial to the mesenchymal state. This process, known as epithelial-mesenchymal transition (EMT), is one of the factors that give the tumor cells greater invasive and migratory capacity with subsequent formation of metastases. In addition, many cancers, including prostate cancer, are derived from a cell population that shows the properties of stem cells.

Resuming Training in High-Level Athletes After Mild COVID-19 Infection: A Multicenter Prospective Study (ASCCOVID-19).

Background: There is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID).

Objectives: The aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes.

Methods: 950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included.

Drives Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer and Tumorigenesis .

Estrogen receptors (ERs) have pivotal roles in the development and progression of triple-negative breast cancer (TNBC). Interactions among cancer cells and tumor microenvironment are orchestrated by the extracellular matrix that is rapidly emerging as prominent contributor of fundamental processes of breast cancer progression. Early studies have correlated ERβ expression in tumor sites with a more aggressive clinical outcome, however ERβ exact role in the progression of TNBC remains to be elucidated.

Heparanase as active player in endothelial glycocalyx remodeling.

The surface of all animal cells is coated with a layer of carbohydrates linked in various ways to the outer side of the plasma membrane. These carbohydrates are mainly bound to proteins in the form of glycoproteins and proteoglycans and together with the glycolipids constitute the so-called glycocalyx. In particular, the endothelial glycocalyx that covers the luminal layer of the endothelium is composed of glycosaminoglycans (heparan sulphate -HS and hyaluronic acid -HA), proteoglycans (syndecans and glypicans) and adsorbed plasma proteins.

EGFR is a pivotal player of the E2/ERβ - mediated functional properties, aggressiveness, and stemness in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is defined by aggressive behavior, limited response to chemotherapy and lower overall survival rates. The increased metastatic potential of TNBC is a combined result of extensive extracellular matrix (ECM) remodeling that leads to cytoskeleton rearrangement and activation of epithelial-to-mesenchymal transition (EMT). The overexpression of epidermal growth factor receptor (EGFR) in TNBC tumors has been linked to induced expression of EMT-related molecules.

Lumican Inhibits In Vivo Melanoma Metastasis by Altering Matrix-Effectors and Invadopodia Markers.

It was reported that lumican inhibits the activity of metalloproteinase MMP-14 and melanoma cell migration in vitro and in vivo. Moreover, Snail triggers epithelial-to-mesenchymal transition and the metastatic potential of cancer cells. Therefore, the aim of this study was to examine the effect of lumican on Mock and Snail overexpressing melanoma B16F1 cells in vivo.

A guide to the composition and functions of the extracellular matrix.

Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell-bound factors are among the major members of the ECM family.

Long filopodia and tunneling nanotubes define new phenotypes of breast cancer cells in 3D cultures.

Cancer cell invasion into the surrounding extracellular matrix (ECM) takes place when cell-cell junctions are disrupted upon epithelial-to-mesenchymal transition (EMT). Both cancer cell-stroma and cell-cell crosstalk are essential to support the continuous tumor invasion. Cancer cells release microvesicles and exosomes containing bioactive molecules and signal peptides, which are recruited by neighboring cells or carried to distant sites, thus supporting intercellular communication and cargo transfer.

miR-200b restrains EMT and aggressiveness and regulates matrix composition depending on ER status and signaling in mammary cancer.

Secreted microRNAs (miRNAs) reside in a complex regulatory network with extracellular matrix (ECM) macromolecules, which affect cell-cell communication, therefore miRNA expression highlights its significance in several aspects of human diseases, including cancer. miRNA-mediated regulation of breast cancer has received considerable attention due to evidence that shows miRNAs to mediate estrogen receptor (ER) status, metastasis, chemoresistance and epithelial-to-mesenchymal transition (EMT). miR-200b is a pluripotent miRNA, which is inversely regulated by ERα and ERβ in mammary cancer.

The action of hyaluronan in functional properties, morphology and expression of matrix effectors in mammary cancer cells depends on its molecular size.

Breast cancer constitutes a heterogeneous disease. The expression profiles of estrogen receptors (ERs), as well as the expression patterns of extracellular matrix (ECM) macromolecules, determine its development and progression. Hyaluronan (HA) is an ECM molecule that regulates breast cancer cells' properties in a molecular size-dependent way.

ΕGFR/ERβ-Mediated Cell Morphology and Invasion Capacity Are Associated with Matrix Culture Substrates in Breast Cancer.

Breast cancer accounts for almost one in four cancer diagnoses in women. Studies in breast cancer patients have identified several molecular markers, indicators of aggressiveness, which help toward more individual therapeutic approaches. In triple-negative breast cancer (TNBC), epidermal growth factor receptor (EGFR) overexpression is associated with increased metastatic potential and worst survival rates.

Extracellular Matrix-Mediated Breast Cancer Cells Morphological Alterations, Invasiveness, and Microvesicles/Exosomes Release.

Breast cancer is a leading disease in women. Several studies are focused to evaluate the critical role of extracellular matrix (ECM) in various biochemical and molecular aspects but also in terms of its effect on cancer cell morphology and therefore on cancer cell invasion and metastatic potential. ECM fibrillar components, such as collagen and fibronectin, affect cell behavior and properties of mammary cancer cells.

Evaluation of lumican effects on morphology of invading breast cancer cells, expression of integrins and downstream signaling.

The small leucine-rich proteoglycan lumican regulates estrogen receptors (ERs)-associated functional properties of breast cancer cells, expression of matrix macromolecules, and epithelial-to-mesenchymal transition. However, it is not known whether the ER-dependent lumican effects on breast cancer cells are related to the expression of integrins and their intracellular signaling pathways. Here, we analyzed the effects of lumican in three breast cancer cell lines: the highly metastatic ERβ-positive MDA-MB-231, cells with the respective ERβ-suppressed (shERβMDA-MB-231), and lowly invasive ERα-positive MCF-7/c breast cancer cells.

Epithelial-to-mesenchymal transition and invadopodia markers in breast cancer: Lumican a key regulator.

A great hallmark of breast cancer is the absence or presence of estrogen receptors ERα and ERβ, with a dominant role in cell proliferation, differentiation and cancer progression. Both receptors are related with Epithelial-to-Mesenchymal Transition (EMT) since there is a relation between ERs and extracellular matrix (ECM) macromolecules expression, and therefore, cell-cell and cell-ECM interactions. The endocrine resistance of ERα endows epithelial cells with increased aggressiveness and induces cell proliferation, resulting into a mesenchymal phenotype and an EMT status.

Role of heparanase in tumor progression: Molecular aspects and therapeutic options.

Heparanase (HPSE) is an endoglycosidase that catalyses the cutting of the side chains of heparan-sulphate proteoglycans (HS), thus determining the remodelling of the extracellular matrix and basement membranes, as well as promoting the release of different HS-related molecules as growth factors, cytokines and enzymes. Ever since the HPSE was identified in the late 1980s, several experimental studies have shown that its overexpression was instrumental in increasing tumor growth, metastatic dissemination, angiogenesis and inflammation. More recently, HPSE involvment has also been demonstrated in mediating tumor-host crosstalk, in inducing gene transcription, in the activation of signaling pathways and in the formation of exosomes and in autophagy.

Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells.

High levels of hyaluronan (ΗΑ), a major extracellular matrix (ECM) glycosaminoglycan, have been correlated with poor clinical outcome in several malignancies, including breast cancer. The high and low molecular weight HΑ forms exert diverse biological functions. Depending on their molecular size, ΗΑ forms either promote or attenuate signaling cascades that regulate cancer progression.

Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells.

Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e.

Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer.

Hyaluronan (HA) is a linear nonsulfated glycosaminoglycan of the extracellular matrix that plays a pivotal role in a variety of biological processes. High-molecular weight HA exhibits different biological properties than oligomers and low-molecular weight HA. Depending on their molecular size, HA fragments can influence cellular behavior in a different mode of action.

Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics.

The extracellular matrix (ECM) constitutes a highly dynamic three-dimensional structural network comprised of macromolecules, such as proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, fibronectin, elastin, other glycoproteins and proteinases. In recent years, the field of PGs has expanded rapidly. Due to their high structural complexity and heterogeneity, PGs mediate several homeostatic and pathological processes.

Estrogen receptor beta as epigenetic mediator of miR-10b and miR-145 in mammary cancer.

Even though the role of estrogen receptor alpha (ERα) in the modulation of breast cancer cells' behavior is thoroughly studied, the biological functions of its isoform, ERβ, are less elucidated. The suppression of ERβ in the aggressive ERα-negative MDA-MB-231 breast cancer cells resulted in the inhibition of epithelial to mesenchymal transition (EMT) and major changes in the basic functional properties and expression levels of certain matrix components of breast cancer cells. This arrest in metastatic potential of breast cancer cells suggests the contribution of ERβ in the induction of a more aggressive phenotype in MDA-MB-231 breast cancer cells.

Lumican effectively regulates the estrogen receptors-associated functional properties of breast cancer cells, expression of matrix effectors and epithelial-to-mesenchymal transition.

Lumican is a small leucine-rich proteoglycan that has been shown to contribute in several physiological processes, but also to exert anticancer activity. On the other hand, it has been recently shown that knockdown of the estrogen receptor α (ERα) in low invasive MCF-7 (ERα+) breast cancer cells and the suppression of ERβ in highly aggressive MDA-MB-231 (ERβ+) cells significantly alter the functional properties of breast cancer cells and the gene expression profile of matrix macromolecules related to cancer progression and cell morphology. In this report, we evaluated the effects of lumican in respect to the ERs-associated breast cancer cell behaviour, before and after suppression of ERs, using scanning electron and confocal microscopies, qPCR and functional assays.