• Title/Summary/Keyword: Cellular microenvironment

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Investigation of Cell-Matrix Interactions Using a FRET Technique

  • Shahbuddin, Munira B.;Park, Hong-Hyun;Lee, Jae-Won;Park, So-Yeon;Lee, Kuen-Yong
    • Bulletin of the Korean Chemical Society
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    • v.30 no.8
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    • pp.1817-1820
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    • 2009
  • Controlling cell-matrix interactions is critical in regulating cell phenotypes for tissue engineering applications. Cellular adhesion to synthetic extracellular matrices (ECMs) can be enhanced by introduction of adhesion ligands to the matrices. We tested the hypothesis that biophysical cues such as ligand organization in synthetic ECMs play an important role in modulating cell responses to the microenvironment. To investigate and monitor cell-matrix interactions, we used a fluorescence resonance energy transfer (FRET) technique with cell-interactive polymers generated by conjugating a peptide with the sequence of arginine-glycine-aspartic acid (RGD) to alginate hydrogels.

Are Macrophages in Tumors Good Targets for Novel Therapeutic Approaches?

  • Alahari, Samthosh V.;Dong, Shengli;Alahari, Suresh K.
    • Molecules and Cells
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    • v.38 no.2
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    • pp.95-104
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    • 2015
  • The development of cancer has been an extensively researched topic over the past few decades. Although great strides have been made in cancer prevention, diagnosis, and treatment, there is still much to be learned about cancer's micro-environmental mechanisms that contribute to cancer formation and aggressiveness. Macrophages, lymphocytes which originate from monocytes, are involved in the inflammatory response and often dispersed to areas of infection to fight harmful antigens and mutated cells in tissues. Macrophages have a plethora of roles including tissue development and repair, immune system functions, and inflammation. We discuss various pathways by which macrophages get activated, various approaches that can regulate the function of macrophages, and how these approaches can be helpful in developing new cancer therapies.

Adult Mesenchymal Stem Cells for Cell Therapy in Clinical Application (임상적용을 위한 세포치료제로서의 성체 중간엽줄기세포)

  • Song, In-Hwan
    • Journal of Yeungnam Medical Science
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    • v.26 no.1
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    • pp.1-14
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    • 2009
  • Human bone marrow-derived mesenchymal stem cells (MSCs) are a rare population of undifferentiated cells that have the capacity of self renewal and the ability to differentiate into mesodermal phenotypes, including osteocytes, chondrocytes, and adipocytes in vitro. Recently, MSCs have been shown to reside within the connective tissue of most organs, and their surface phenotype has been well analyzed. Many reports showed that transplanted MSCs enhanced regeneration as well as functional improvement of damaged organs and tissues. The wide differentiation plasticity of MSCs was expected to contribute to their demonstrated efficacy in a wide variety of experimental animal models and in human clinical trials. However, new findings suggest that the ability of MSCs to alter the tissue microenvironment via secretion of soluble factors may contribute more significantly than their capacity for differentiation in tissue repair. This review describes what is known about the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for further applications in regenerative medicine.

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Diagnostic Significance of pH-Responsive Gd3+-Based T1 MR Contrast Agents

  • Bhuniya, Sankarprasad;Hong, Kwan Soo
    • Investigative Magnetic Resonance Imaging
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    • v.23 no.1
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    • pp.17-25
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    • 2019
  • We discuss recent advances in Gd-based $T_1$-weighted MR contrast agents for the mapping of cellular pH. The pH plays a critical role in various biological processes. During the past two decades, several MR contrast agents of strategic importance for pH-mapping have been developed. Some of these agents shed light on the pH fluctuation in the tumor microenvironment. A pH-responsive self-assembled contrast agent facilitates the visualization of tumor size as small as $3mm^3$. Optimization of various parameters is crucial for the development of pH-responsive contrast agents. In due course, the new contrast agents may provide significant insight into pH fluctuations in the human body.

Autophagy in the uterine vessel microenvironment: Balancing vasoactive factors

  • Lim, Hyunjung Jade
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.4
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    • pp.263-268
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    • 2020
  • Autophagy, which has the literal meaning of self-eating, is a cellular catabolic process executed by arrays of conserved proteins in eukaryotes. Autophagy is dynamically ongoing at a basal level, presumably in all cells, and often carries out distinct functions depending on the cell type. Therefore, although a set of common genes and proteins is involved in this process, the outcome of autophagic activation or deficit requires scrutiny regarding how it affects cells in a specific pathophysiological context. The uterus is a complex organ that carries out multiple tasks under the influence of cyclic changes of ovarian steroid hormones. Several major populations of cells are present in the uterus, and the interactions among them drive complex physiological tasks. Mouse models with autophagic deficits in the uterus are very limited, but provide an initial glimpse at how autophagy plays a distinct role in different uterine tissues. Herein, we review recent research findings on the role of autophagy in the uterine mesenchyme in mouse models.

Classifying the Linkage between Adipose Tissue Inflammation and Tumor Growth through Cancer-Associated Adipocytes

  • Song, Yae Chan;Lee, Seung Eon;Jin, Young;Park, Hyun Woo;Chun, Kyung-Hee;Lee, Han-Woong
    • Molecules and Cells
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    • v.43 no.9
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    • pp.763-773
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    • 2020
  • Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

Up-regulation of Insulin-like Growth Factor Binding Protein-3 Is Associated with Brain Metastasis in Lung Adenocarcinoma

  • Yang, Lishi;Li, Junyang;Fu, Shaozhi;Ren, Peirong;Tang, Juan;Wang, Na;Shi, Xiangxiang;Wu, Jingbo;Lin, Sheng
    • Molecules and Cells
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    • v.42 no.4
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    • pp.321-332
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    • 2019
  • The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

Suppressive Effects of an Ishige okamurae extract on 3T3-L1 Preadipocyte Differentiation

  • Cha, Sun-Yeong;Cheon, Yong-Pil
    • Development and Reproduction
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    • v.17 no.4
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    • pp.451-459
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    • 2013
  • The biological activity of tissue specific stem cell is under the control of their specific microenvironment and the exogenous chemicals derived from digestive tract can be one of the constructing factors of that. It is suggested that the extract of brown algae Ishige okamurae has antioxidant-, apoptosis induction-, and antiinflammatory-effects. On the other hand, a few studies have shown that antioxidant assist inhibition of accumulation of fat. So we studied the effect of the extract of I. okamura on the cellular activity and differentiation of 3T3-L1 preadipocyte to adipose cell. The viability of cell was analyzed using 3-[4,5-dimethylthiazo-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Adipogenesis of 3T3-L1 cell was analyzed after induction in the induction medium containing the I. okamurae extract. The cellular activity was high compared with the vehicle and 0.05 mM caffeine in all groups of I. okamurae extract treated cells. The extract of I. okamura inhibited accumulation of lipids in 10 and $50{\mu}g/ml$. The expression of the marker genes for adipocyte differentiation coincided with cytochemical results. These results suggest that the extract of I. okamurae increases the cellular viability of adipose precursor cells. On the other hand, it suppresses the differentiation of preadipocyte to adipocyte and accumulation of lipids in concentration-dependent manners. It may be possible that the major component of the extract can be applied in the control of adipose tissuegenesis.

Infectivity of Orientia tsutsugamushi to Various Eukaryotic Cells and Their Cellular Invasion Mechanism (Orientia tsutsugamushi의 유핵세포내 감염능 분석 및 기전)

  • Ihn, Kyung-Soo;Han, Seung-Hoon;Kim, Hang-Rae;Seong, Seung-Yong;Kim, Ik-Sang;Choi, Myung-Sik
    • The Journal of the Korean Society for Microbiology
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    • v.34 no.5
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    • pp.435-443
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    • 1999
  • Orientia tsutsugamushi is obligate intracellular bacterium that grows within the cytoplasm of the eukaryotic host cells. Therefore capability of the attachment, entry into the host cell and intracellular survival should be critical process for oriential infection. In this study we investigated the cellular invasion mechanism of Orientia tsutsugamushi and the role of transmembrane heparan sulfate proteoglycan, which binds diverse components at the cellular microenvironment and is implicated as host cell receptors for a variety of microbial pathogens. First of all Orientia tsutsugamushi can invade a wide range of nonprofessional phagocytic cells including fibroblast, epithelial cells and endothelial cells of various host species, including Band T lymphocytes. Thus, it was postulated that the attachment of O. tsutsugamushi requires the recognition of ubiquitous surface structures of many kinds of host cells. Treatments with heparan sulfate and heparin inhibited the infection of Orientia tsutsugamushi in dose-dependent manner for L cell, mouse fibroblast, whereas other glycosaminoglycans such as chondroitin sulfate had no effect. Collectively, these findings provide strong evidence that initial interaction with heparan sulfate proteoglycan is required for the oriential invasion into host cells.

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IMMUNOHISTOCHEMICAL ANALYSIS OF EGFR AND C-ERB-B2 GENE EXPRESSION OF SQUAMOUS CELL CARCINOMA IN ORAL CAVITY (구강 편평세포암에서 EGFR과 C-erb-B2 유전자 발현에 관한 면역조직화학적 연구)

  • Cho, Won;Cho, Jae-Shik;Lee, Chong-Won;Kim, Hae-Song;Park, Guen-Jae
    • Korean Journal of Bronchoesophagology
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    • v.2 no.2
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    • pp.200-212
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    • 1996
  • The clinical staging systems for oral squamous cell carcinoma is limited as a prognostic indicatior because of different biological characteristics of cancer in this region and variable microenvironment depending on subsites, there have been study to determine prognosis by evaluating malignancy, that is the nature of tumor cells. Many studies have been tried to determine prognostic indicator in various malignancies for the evaluation of differentiation capacity and the expression of oncogene product. EGF make a role in cellular growth and differentiation and to be essential in cellular survival. EGFR is an intergral membrane protein, stimulate cellular differentiation and hormonal secretion, and has structural homology with V-erb-B transforming protein. Recent reports have demonstrated that EGFR is overexpressed in stomach, breast, vagina, dermis, head and neck, genitourinary and lung tumors, and possibly used as a tumor marker. In head and neck region, most of studies were mainly carried out on laryngeal squamous cell carcinoma. In the present study, immunohistochemical study for EGFR and C-erb-B2 gene in paraffin sections of 45 squamous cell carcinoma in oral cavity was performed to evaluate the presense of EGFR and C- erb-B2 gene in this lesion, to evaluate them as a prognostic indicator by analysing the correlation between these expression and subsites, primary stages, clinical stages, pathologic grades, neck node metastasis, recurrences and treatment results, and to determine relation between EGFR and C-erb-B2 gene.

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