Atomic force microscopy reveals the influence of substrate collagen concentration and TGF-β on lung fibroblast mechanics.

Understanding how extracellular matrix (ECM) stiffness and biochemical factors such as TGF-β affect cell behaviour is critical for elucidating mechanisms underlying several pathologic conditions such as tissue fibrosis and cancer metastasis. This study investigates the effects of varying collagen substrate concentration and consequently varying stiffness conditions along with TGF-β treatment on the morphology, nanomechanical properties, and gene expression of normal human lung fibroblasts (NHLF). Our results reveal that increased substrate stiffness leads to more elongated cell morphology, decreased cellular stiffness, and significant alterations in gene expression related to cytoskeletal organization and myofibroblast activation genes.

Assessing sarcoma cell cytoskeleton remodeling in response to varying collagen concentration.

Sarcomas, rare malignant tumors of mesenchymal origin, are often underdiagnosed and have face diagnostic ambiguities and limited treatment options. The main objective of this study was to define the nanomechanical and biophysical properties of sarcoma cells, particularly examining how the cytoskeleton's remodeling and related cellular processes such as cell migration and invasion in response to environmental stimuli due to collagen content. Utilizing one murine fibrosarcoma and one osteosarcoma cell line we employed atomic force microscopy, immunostaining, advanced image processing, in vitro cellular assays, and molecular techniques to investigate cells' cytoskeleton remodeling in response to varying collagen concentration.

Phytochemical Profiles and Biological Activities of Plant Extracts from Aromatic Plants Cultivated in Cyprus.

Medicinal and aromatic plants' properties, still an interesting research area, are attributed to the presence of various specialized products that possess important pharmacological activities. In the present study, six medicinal/aromatic plants (, , , , , and ) were evaluated for their phytochemical and nutritive composition, as well as their biological activities, including antioxidant, antimicrobial, and cytotoxic properties. The results obtained indicate that was rich in proteins and minerals such as N and Mg, while accumulated more K, Na, P, and Ca.

Midkine (MDK) in Hepatocellular Carcinoma: More than a Biomarker.

Midkine (MDK) is a multifunctional secreted protein that can act as a cytokine or growth factor regulating multiple signaling pathways and being implicated in fundamental cellular processes, such as survival, proliferation, and migration. Although its expression in normal adult tissues is barely detectable, MDK serum levels are found to be elevated in several types of cancer, including hepatocellular carcinoma (HCC). In this review, we summarize the findings of recent studies on the role of MDK in HCC diagnosis and progression.

Fascin-1 in Cancer Cell Metastasis: Old Target-New Insights.

As metastasis is responsible for most cancer-related deaths, understanding the cellular and molecular events that lead to cancer cell migration and invasion will certainly provide insights into novel anti-metastatic therapeutic targets. Fascin-1 is an actin-bundling protein fundamental to all physiological or pathological processes that require cell migration. It is responsible for cross-linking actin microfilaments during the formation of actin-rich cellular structures at the leading edge of migrating cells such as filopodia, lamellipodia and invadopodia.

Ras suppressor 1 long form (RSU1L) silencing promotes apoptosis in invasive breast cancer cells.

Ras Suppressor-1 (RSU1) is a cell-extracellular matrix (ECM) adhesion protein implicated in breast cancer (BC) cell metastasis. Nevertheless, its role in apoptosis is yet unknown. In the present study, we used bioinformatics tools to evaluate the association of RSU1 expression and BC patient survival, the expression of basic pro- and anti-apoptotic genes in metastatic BC samples and their correlation with the expression of RSU1.

Effects of 2-methoxyestradiol on hydrogen peroxide induced neuronal cell death and tau hyperphosphorylation.

Aims: Alzheimer's Disease (AD) is characterized by progressive cognitive impairment, and memory loss. It has been shown that depletion of estrogens renders women vulnerable to AD with menopause women presenting higher risk for AD development than men. However, women under hormone replacement therapy (HRT) with 17β-estradiol (E2) show lower risk for AD, implying that E2 may be protective.

LincRNAs and snoRNAs in Breast Cancer Cell Metastasis: The Unknown Players.

Recent advances in research have led to earlier diagnosis and targeted therapies against breast cancer, which has resulted in reduced breast cancer-related mortality. However, the majority of breast cancer-related deaths are due to metastasis of cancer cells to other organs, a process that has not been fully elucidated. Among the factors and genes implicated in the metastatic process regulation, non-coding RNAs have emerged as crucial players.

The focal adhesion protein Integrin-Linked Kinase (ILK) as an important player in breast cancer pathogenesis.

Cell-extracellular matrix interactions, or focal adhesions (FA), are crucial for tissue homeostasis but are also implicated in cancer. Integrin-Linked Kinase (ILK) is an abundantly expressed FA protein involved in multiple signaling pathways. Here, we reviewed the current literature on the role of ILK in breast cancer (BC).

Ras Suppressor-1 (RSU1) in Cancer Cell Metastasis: A Tale of a Tumor Suppressor.

Cancer is a multifactorial disease responsible for millions of deaths worldwide. It has a strong genetic background, as mutations in oncogenes or tumor suppressor genes contribute to the initiation of cancer development. Integrin signaling as well as the signaling pathway of oncogene, have been long implicated both in carcinogenesis and disease progression.

ILK silencing inhibits migration and invasion of more invasive glioblastoma cells by downregulating ROCK1 and Fascin-1.

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor and it is associated with poor survival. Integrin-linked kinase (ILK) is a serine/threonine protein pseudo-kinase that binds to the cytoplasmic domains of β1 and β3 integrins and has been previously shown to promote invasion and metastasis in many cancer types, including GBM. However, little is known regarding the exact molecular mechanism implicating ILK in GBM aggressiveness.

Growth differentiation factor 15 (GDF15) in cancer cell metastasis: from the cells to the patients.

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β superfamily, has been postulated to be implicated in cancer cell metastasis although its role has not been fully elucidated yet. The purpose of this review is to clarify the role of GDF-15 in cancer cell metastasis based on current advances in the field. The studies were divided into those involving evaluation of GDF15 expression in the serum or tissue of cancer patients, and those involving in vitro experiments in cancer cell lines or in vivo experiments in animal models.

Silencing of Growth Differentiation Factor-15 Promotes Breast Cancer Cell Invasion by Down-regulating Focal Adhesion Genes.

Background/aim: As metastasis accounts for most breast cancer (BC)-related deaths, identifying key players becomes research priority. Growth differentiation factor-15 (GDF15), a member of the transforming growth factor-β superfamily, is affected by the actin cytoskeleton and has been associated with cancer. However, its exact role in BC cell invasiveness is vague.

Coordinated Expression of Ras Suppressor 1 (RSU-1) and Growth Differentiation Factor 15 (GDF15) Affects Glioma Cell Invasion.

Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor due to its invasive phenotype. Ras suppressor 1 (RSU-1) is a cell-extracellular matrix adhesion protein and we recently found that it promotes cell invasion in aggressive cells and inhibits it in non-invasive. Growth differentiation factor-15 (GDF15) is known to be involved in actin cytoskeleton reorganization and metastasis.

Depletion of Ras Suppressor-1 (RSU-1) promotes cell invasion of breast cancer cells through a compensatory upregulation of a truncated isoform.

Extracellular matrix (ECM)-adhesion proteins and actin cytoskeleton are pivotal in cancer cell invasion. Ras Suppressor-1 (RSU-1), a cell-ECM adhesion protein that interacts with PINCH-1, thus being connected to Integrin Linked Kinase (ILK), alpha-parvin (PARVA), and actin cytoskeleton, is up-regulated in metastatic breast cancer (BC) samples. Apart from the originally-identified gene (RSU-1L), an alternatively-spliced isoform (RSU-1-X1) has been reported.

Ras suppressor-1 (RSU-1) promotes cell invasion in aggressive glioma cells and inhibits it in non-aggressive cells through STAT6 phospho-regulation.

Most gliomas are invasive tumors formed from glial cells and associated with high mortality rates. In this study, we characterized four glioma cell lines of varying degree of aggressiveness (H4, SW1088, A172 and U87-MG) in terms of morphology, cytoskeleton organization and stiffness, and evaluated their invasive potential by performing invasion, colony forming and spheroid invasion assays. Cells were divided into two distinct groups: aggressive cell lines (A172 and U87-MG) with more elongated, softer and highly invasive cells and less aggressive cells (H4 and SW088).

Collagen content and extracellular matrix cause cytoskeletal remodelling in pancreatic fibroblasts.

In many solid tumours a desmoplastic reaction takes place, which results in tumour tissue stiffening due to the extensive production of extracellular matrix (ECM) proteins, such as collagen, by stromal cells, mainly fibroblasts (FBs) and cancer-associated fibroblasts (CAFs). In this study, we investigated the effect of collagen stiffness on pancreatic FBs and CAFs, particularly on specific cytoskeleton properties and gene expression involved in tumour invasion. We found that cells become stiffer when they are cultured on stiff substrates and express higher levels of alpha-smooth muscle actin (α-SMA).

Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15).

Extracellular matrix (ECM)-related adhesion proteins are important in metastasis. Ras suppressor-1 (RSU-1), a suppressor of -transformation, is localized to cell⁻ECM adhesions where it interacts with the Particularly Interesting New Cysteine-Histidine rich protein (PINCH-1), being connected to Integrin Linked Kinase (ILK) and alpha-parvin (PARVA), a direct actin-binding protein. was also found upregulated in metastatic breast cancer (BC) samples and was recently demonstrated to have metastasis-promoting properties.

The role of fibroblast growth factors and their receptors in gliomas: the mutations involved.

The central nervous system (CNS) comprises of neurons, which are responsible for impulse transmission, and glial cells, which surround neurons providing protection and nutrition. Glial cells are categorized into astrocytes, oligodendrocytes, microglial cells, and ependymal cells. Tumors forming from glial cells are called gliomas, and they are classified accordingly into astrocytomas, oligodendrogliomas, and ependymomas.

Atomic force microscopy nano-characterization of 3D collagen gels with tunable stiffness.

As extracellular matrix (ECM) nano-characteristics play a crucial role in cell behavior, including cancer development and metastasis, several ECM in vitro models have been used in order to study cells behavior under different biochemical and mechanical conditions. Among the ECM constituents, collagen (especially collagen type I) has been extensively used as an essential component of ECM models, since it is one of the most abundant ECM protein. Use of three-dimensional (3D) collagen gels provides the advantage of allowing the cells to grow in a 3D environment that bears strong similarities to their natural, in vivo setting.

Cell Adhesion and Matrix Stiffness: Coordinating Cancer Cell Invasion and Metastasis.

Metastasis is a multistep process in which tumor extracellular matrix (ECM) and cancer cell cytoskeleton interactions are pivotal. ECM is connected, through integrins, to the cell's adhesome at cell-ECM adhesion sites and through them to the actin cytoskeleton and various downstream signaling pathways that enable the cell to respond to external stimuli in a coordinated manner. Cues from cell-adhesion proteins are fundamental for defining the invasive potential of cancer cells, and many of these proteins have been proposed as potent targets for inhibiting cancer cell invasion and thus, metastasis.

Transforming growth factor-β modulates pancreatic cancer associated fibroblasts cell shape, stiffness and invasion.

Background: Tumor microenvironment consists of the extracellular matrix (ECM), stromal cells, such as fibroblasts (FBs) and cancer associated fibroblasts (CAFs), and a myriad of soluble factors. In many tumor types, including pancreatic tumors, the interplay between stromal cells and the other tumor microenvironment components leads to desmoplasia, a cancer-specific type of fibrosis that hinders treatment. Transforming growth factor beta (TGF-β) and CAFs are thought to play a crucial role in this tumor desmoplastic reaction, although the involved mechanisms are unknown.

Solid Stress Facilitates Fibroblasts Activation to Promote Pancreatic Cancer Cell Migration.

Pancreatic fibroblasts are continuously gaining ground as an important component of tumor microenvironment that dynamically interact with cancer cells to promote tumor progression. In addition, these tumor-infiltrated fibroblasts can acquire an activated phenotype and produce excessive amounts of extracellular matrix creating a highly dense stroma, a situation known as desmoplasia. Desmoplasia, along with the uncontrolled proliferation of cancer cells, leads to the development of compressive forces within the tumor, generating the so-called solid stress.