Publications by authors named "Berrin Ozdil"

8 Publications

  • Page 1 of 1

CD133+/CD44+ prostate cancer stem cells exhibit embryo-like behavior patterns.

Acta Histochem 2021 Jul 20;123(5):151743. Epub 2021 Jun 20.

Van Yuzuncu Yil University, Faculty of Medicine, Van, Turkey.

Cancer stem cells (CSCs), which act as an important bridge between cancer formation and embryonic development, represent a small population associated with tumor initiation, drug resistance, metastasis and recurrence. CSCs have the ability to form spheroids in three-dimensional culture systems. Tumor spheroids derived from CSCs with symmetric and asymmetric division patterns were found to contain highly heterogeneous cell groups. The biological behavior patterns which some CSCs display serve as an important bridge between cancer formation and embryonic development. The cell population in the DU-145 prostate cancer cell line with surface markers CD133+/CD44+ was isolated by FACS. Prostate spheroids were formed by using agarose-coated plates. The morphological characteristics of the cell population within spheroid structure and the expression of Ki-67 and Caspase-3 were investigated by histochemical methods. In this study, we observed that CD133+/CD44+ prostate CSCs form different spheroid structures as well as normal spheroid structures: i) some spheroid structures formed with a highly transparent zone on the outer part of the spheroid, in addition to the normal spheroidal zones and ii) spheroidal structures obtained from prostate CD1334+/CD44+ CSCs that share the same microenvironment are hollow spheres similar to the blastula-like structure in the embryo. These spheroidal structures exhibiting embryo-like properties indicate that the expression of embryonic factors might be reiterated in CSCs. Further investigation of the formation mechanism of the transparent zone and the hollow sphere will shed light on the embryonic origin of prostate cancer and the design of new therapeutic strategies.
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http://dx.doi.org/10.1016/j.acthis.2021.151743DOI Listing
July 2021

The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells.

Turk J Biol 2021 9;45(1):26-34. Epub 2021 Feb 9.

Department of Medical Biology, Faculty of Medicine, Ege University, İzmir Turkey.

PIKfyve is an evolutionarily conserved lipid and protein kinase enzyme that has pleiotropic cellular functions. The aim of the present study was to investigate the effects of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) inhibitor, YM201636, on nonsmall cell lung cancer (NSCLC) cells growth, tumorigenicity, and claudin (CLDN) expressions. Three NSCLC cell lines (Calu-1, H1299 and HCC827) were used to compare the effects of YM201636. Cytotoxic effects of YM201636 were analysed using XTT assay. Malignancy potential of cells assesses with wound healing and soft agar colony-forming assays. mRNA and protein expressions of claudins were analysed by qRT-PCR and immunofluorescence staining. Our results revealed that YM201636 inhibited the proliferation and malignancy potential of Calu-1, H1299, and HCC827 cells in a dose-dependent manner. After YM201636 treatment CLDN1, -3 and -5 expressions increased significantly in HCC827 cells. CLDN3 and -5 expressions also significantly increased in Calu1 cell line. YM201636 treatment significantly reduced the CLDN1 and increased the CLDN5 expression in H1299 cells. Immunofluorescence staining of CLDN1, -3 and -5 proteins showed a significant increase after YM201636 treatment. Besides, YM201636 induced EGFR mRNA expression in all NSCLC cell lines. Our results have shown that YM201636 inhibits tumorigenicity of NSCLC cells. Furthermore, estimated glomerular filtration rate (EGFR) pathway is important signalling involved in the regulation of claudins. Understanding the mechanisms of PIKfyve inhibitors may improve cancer treatment particularly for EGFR overactivated NSCLC.
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http://dx.doi.org/10.3906/biy-2010-32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877718PMC
February 2021

Holistic Approach to Cell Characteristics and Behavioral Analysis.

Crit Rev Oncog 2019 ;24(1):21-26

Department of Histology and Embryology, Ege University, Izmir, Turkey; Department of Histology and Embryology, Yüzüncü Yil University, Van, Turkey.

Cancer is a group of diseases of our era that affects not only medical status but also lowers the tone of social and emotional well-being. It also has severe impacts on economies. Cancer cells are linked to the somatic cells and stem cells, with their characteristic similarities and differences. Variations in cell-signaling pathways, such as cell death and proliferation balances, kinetic behavior of the cells, and their differentiation potentials, are the featured parameters for therapeutic targeting. The detection of target points should be based not only on the molecular biology methods but also on the physical and topological analyses from the aspect of "geography is fate". In this review, we focus on the importance of the holistic analyses of intracellular and extracellular dynamics and multidisciplinary cooperation.
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http://dx.doi.org/10.1615/CritRevOncog.2019029527DOI Listing
July 2020

The effect of extracellular matrix on the differentiation of mouse embryonic stem cells.

J Cell Biochem 2020 01 6;121(1):269-283. Epub 2019 Jun 6.

Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, Turkey.

Embryonic stem cells (ESCs) are promising research materials to investigate cell fate determination since they have the capability to differentiate. Stem cell differentiation has been extensively studied with various microenvironment mimicking structures to modify cellular dynamics associated with the cell-extracellular matrix (ECM) interactions and cell-cell communications. In the current study, our aim was to determine the effect of microenvironmental proteins with different concentrations on the capacity and differentiation capability of mouse ESCs (mESCs), combining the biochemical assays, imaging techniques, Fourier transform infrared (FTIR) spectroscopy, and unsupervised multivariate analysis. Based on our data, coating the surface of mESCs with Matrigel, used as an acellular matrix substrate, resulted in morphological and biochemical changes. mESCs exhibited alterations in their phenotype after growing on the Matrigel-coated surfaces, including their differentiation capacity, cell cycle phase pattern, membrane fluidity, and metabolic activities. In conclusion, mESCs can be stimulated physiologically, chemically, or mechanically to convert them a new phenotype. Thus, identification of ESCs' behavior in the acellular microenvironment could be vital to elucidate the mechanism of diseases. It might also be promising to control the cell fate in the field of tissue engineering.
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http://dx.doi.org/10.1002/jcb.29159DOI Listing
January 2020

Autophagy and mTOR pathways in mouse embryonic stem cell, lung cancer and somatic fibroblast cell lines.

J Cell Biochem 2019 10 30;120(10):18066-18076. Epub 2019 May 30.

Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, Turkey.

Embryonic developmental stages and regulations have always been one of the most intriguing aspects of science. Since the cancer stem cell discovery, striking for cancer development and recurrence, embryonic stem cells and control mechanisms, as well as cancer cells and cancer stem cell control mechanisms become important research materials. It is necessary to reveal the similarities and differences between somatic and cancer cells which are formed of embryonic stem cells divisions and determinations. For this purpose, mouse embryonic stem cells (mESCs), mouse skin fibroblast cells (MSFs) and mouse lung squamous cancer cells (SqLCCs) were grown in vitro and the differences between these three cell lines signalling regulations of mechanistic target of rapamycin (mTOR) and autophagic pathways were demonstrated by immunofluorescence and real-time polymerase chain reaction. Expressional differences were clearly shown between embryonic, cancer and somatic cells that mESCs displayed higher expressional level of Atg10, Hdac1 and Cln3 which are related with autophagic regulation and Hsp4, Prkca, Rhoa and ribosomal S6 genes related with mTOR activity. LC3 and mTOR protein levels were lower in mESCs than MSFs. Thus, the mechanisms of embryonic stem cell regulation results in the formation of somatic tissues whereas that these cells may be the causative agents of cancer in any deterioration.
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http://dx.doi.org/10.1002/jcb.29110DOI Listing
October 2019

Differentiation of Normal and Cancer Cell Adhesion on Custom Designed Protein Nanopatterns.

Nano Lett 2015 Aug 7;15(8):5393-403. Epub 2015 Jul 7.

Department of Molecular Biology and Genetics, Izmir Institute of Technology, 35430 Urla/Izmir, Turkey.

Cell adhesion to the extracellular matrix is deregulated in metastasis. However, traditional surfaces used to study cell adhesion do not faithfully mimic the in vivo microenvironment. Electron beam lithography (EBL) is able to generate customized protein nanopatterns. Here, we used an EBL-based green lithography approach to fabricate homogeneous and gradient, single (fibronectin, K-casein) and double (fibronectin, laminin) active component protein nanopatterns with micrometer scale spacing to investigate differences in adhesion of breast cancer cells (BCC) and normal mammary epithelial cells (NMEC). Our results showed that as expected, in contrast to NMEC, BCC were plastic: they tolerated nonadhesion promoting regions, adapted to flow and exploited gradients better. In addition, the number of focal adhesions but not their area appeared to be the dominant parameter for regulation of cell adhesion. Our findings also demonstrated that custom designed protein nanopatterns, which can properly mimic the in vivo microenvironment, enable realistic distinction of normal and cancerous cell adhesion.
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http://dx.doi.org/10.1021/acs.nanolett.5b01785DOI Listing
August 2015

Fabrication of 3D Controlled in vitro Microenvironments.

MethodsX 2014 8;1:60-6. Epub 2014 Jul 8.

Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Izmir, Turkey.

Microfluidics-based lab-on-a-chips have many advantages, one of which is to provide physiologically relevant settings for cell biology experiments. Thus there is an ever increasing interest in their fabrication. Our goal is to construct three dimensional (3D) Controlled in vitro Microenvironments (CivMs) that mimic the in vivo microenvironments. Here, we present our optimized fabrication method that works for various lab-on-a-chip designs with a wide range of dimensions. The most crucial points are:•While using one type of SU-8 photoresist (SU-2075), fine tuning of ramp, dwell time, spin speed, durations of soft bake, UV exposure and development allows fabrication of SU-8 masters with various heights from 40 to 600 μm.•Molding PDMS (polydimethylsiloxane) at room temperature for at least two days instead of baking at higher temperatures prevents not only tears and bubbles in PDMS stamps but also cracks in the SU-8 master.•3D nature of the CivMs is ensured by keeping the devices inverted during gel polymerization.
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http://dx.doi.org/10.1016/j.mex.2014.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472850PMC
July 2015

Step-by-step quantitative analysis of focal adhesions.

MethodsX 2014 7;1:56-9. Epub 2014 Jul 7.

Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Izmir, Turkey.

Focal adhesions (FAs) are specialized adhesive structures which serve as cellular communication units between cells and the surrounding extracellular matrix. FAs are involved in signal transduction and actin cytoskeleton organization. FAs mediate cell adhesion, which is a critical phenomenon in cancer research. Since cells can form many and micrometer scale FAs, their quantitative analysis demands well-optimized image analysis approaches [1-3]. Here, we have optimized the analysis of FAs of MDA-MB-231 breast cancer cells. The optimization is based on proper processing of immunofluorescence images of vinculin, which is one of the markers of FAs. All image processing steps are carried out using the ImageJ software, which is freely available and in the public domain. The advantages of our method are:•The analysis steps are simplified by combining different plugins of the ImageJ program.•FAs are better detected with minimal false negatives due to optimized processing of fluorescent images.•This approach can be applied to quantify a variety of fluorescent images comprising focal and/or localized signals within a high background such as FAs, one of the many complex signaling structures in a cell.
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http://dx.doi.org/10.1016/j.mex.2014.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472847PMC
July 2015
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