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Zengli Zhang, Huiqian Wang, Qifeng Ding, Yufei Xing, Zhonghua Xu, Chun Lu, Dongdong Luo, Longjiang Xu, Wei Xia, Caicun Zhou, Minhua Shi
The prognosis of advanced non-small cell lung cancer (NSCLC) patients is poor. One of the reasons for this hampered progress has been a lack of in vitro models that would faithfully recapitulate the heterogeneity of tumors and response to treatment. In this study, surgically resected tumors were obtained from patients with stage I/II NSCLC during curative-intent surgery. Using a 3D patient-derived tumor spheroids culture system, our results demonstrate successful long-term expansion of primary NSCLC cells in vitro (> 120 days)...
2018: PloS One
Bárbara da Silva, Ryan K Mathew, Euan S Polson, Jennifer Williams, Heiko Wurdak
Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs)...
March 1, 2018: SLAS Discovery
Omkara Swami Muddineti, Preeti Kumari, Balaram Ghosh, Swati Biswas
PURPOSE: Transferrin receptor (TfR) is up-regulated in various malignant tumors not only to meet the iron requirement, but also to increase the cell survival via participation in various cellular signaling pathways. Here we explored transferrin as ligand for Poly(ethylene Glycol) (PEG)-ylated vitamin-E/lipid (PE) core micelles (VPM). METHODS: Transferrin modified polymer was synthesized and drug loaded micelles were evaluated in 2D Hela and HepG2 cancer cells for cellular uptake and cytotoxicity and in 3D Hela spheroids for growth inhibition, uptake and penetration studies...
March 14, 2018: Pharmaceutical Research
Takahiro Yoshida, Nikolai A Sopko, Max Kates, Xiaopu Liu, Gregory Joice, David J McConkey, Trinity J Bivalacqua
There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells...
February 16, 2018: Oncotarget
Tulika Mitra, Parash Prasad, Pritha Mukherjee, Susri Ray Chaudhuri, Urmi Chatterji, Sib S Roy
Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells...
March 14, 2018: Journal of Cellular Biochemistry
Sara Žigon-Branc, Ariana Barlič, Miomir Knežević, Matjaž Jeras, Gordana Vunjak-Novakovic
Inflammation plays a major role in progression of rheumatoid arthritis (RA), a disease treated with antagonists of tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors...
March 14, 2018: Biotechnology Progress
Gary Hin-Fai Yam, Ericia Pei-Wen Teo, Melina Setiawan, Matthew J Lovatt, Nur Zahirah Binte M Yusoff, Matthias Fuest, Bee-Tin Goh, Jodhbir S Mehta
Corneal opacities are a leading cause of global blindness. They are conventionally treated by the transplantation of donor corneal tissue, which is, restricted by a worldwide donor material shortage and allograft rejection. Autologous adult stem cells with a potential to differentiate into corneal stromal keratocytes (CSKs) could offer a suitable choice of cells for regenerative cell therapy. Postnatal periodontal ligament (PDL) contains a population of adult stem cells, which has a similar embryological origin as CSK, that is cranial neural crest...
March 13, 2018: Journal of Cellular and Molecular Medicine
Wei Zhang, Luc Girard, Yu-An Zhang, Tomohiro Haruki, Mahboubeh Papari-Zareei, Victor Stastny, Hans K Ghayee, Karel Pacak, Trudy G Oliver, John D Minna, Adi F Gazdar
Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models...
February 2018: Translational Lung Cancer Research
Julien Daubriac, Shiwei Han, Jelena Grahovac, Eve Smith, Abdel Hosein, Marguerite Buchanan, Mark Basik, Yves Boucher
Carcinoma-associated fibroblasts (CAFs) can remodel the extracellular matrix to promote cancer cell invasion, but the paracrine signaling between CAFs and cancer cells that regulates tumor cell migration remains to be identified. To determine how the interaction between CAFs and cancer cells modulates the invasiveness of cancer cells, we developed a 3-dimensional co-culture model composed of breast cancer (BC) MDA-MB-231 cell spheroids embedded in a collagen gel with and without CAFs. We found that the crosstalk between CAFs and cancer cells promotes invasion by stimulating the scattering of MDA-MB-231 cells, which was dependent on RhoA/ROCK/phospho MLC signaling in cancer cells but independent of RhoA in CAFs...
February 13, 2018: Oncotarget
Jue Hou, Joshua Williams, Elliot Botvinick, Eric Potma, Bruce J Tromberg
Label-free non-linear optical microscopy (NLOM) based on two-photon excited fluorescence (TPEF) from cofactors Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD+) is widely used for high-resolution cellular redox imaging. In this work, we combined three, label-free NLOM imaging methods to quantitatively characterize breast cancer cells and their relative invasive potential: 1) TPEF optical redox ratio (ORR = FAD+/NADH + FAD+), 2) coherent Raman scattering (CRS) of cellular lipids, and 3) second harmonic generation (SHG) of extracellular matrix (ECM) collagen...
March 13, 2018: Cancer Research
Pingyu Nan, Darragh M Walsh, Kerry A Landman, Barry D Hughes
Motivated by in vitro time-lapse images of ovarian cancer spheroids inducing mesothelial cell clearance, the traditional agent-based model of cell migration, based on simple volume exclusion, was extended to include the possibility that a cell seeking to move into an occupied location may push the resident cell, and any cells neighbouring it, out of the way to occupy that location. In traditional discrete models of motile cells with volume exclusion such a move would be aborted. We introduce a new shoving mechanism which allows cells to choose the direction to shove cells that expends the least amount of shoving effort (to account for the likely resistance of cells to being pushed)...
2018: PloS One
K L Middlemiss, D G Cook, A R Jerrett, W Davison
Schooling behaviour in yellow-eyed mullet Aldrichetta forsteri, a common fish species in New Zealand estuarine habitats, was investigated to identify interaction rules associated with group formation. Tank-based three-dimensional studies of three group sizes (15, 75 and 150 individuals) were carried out to measure the effects of these different group sizes on school structure during control, predation risk and foraging behavioural states. Increased group size positively correlated with nearest-neighbour distance in control and foraging states...
March 12, 2018: Journal of Fish Biology
Maria F Gencoglu, Lauren E Barney, Christopher L Hall, Elizabeth A Brooks, Alyssa D Schwartz, Daniel C Corbett, Kelly R Stevens, Shelly R Peyton
Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Multicellular tumor spheroids (MCTS) are a popular method for three-dimensional (3D) cell culture, because they capture some aspects of the dimensionality, cell-cell contact, and cell-matrix interactions seen in vivo. Many approaches exist to create MCTS from cell lines, and they have been used to study tumor cell invasion, growth, and how cells respond to drugs in physiologically relevant 3D microenvironments...
February 12, 2018: ACS Biomaterials Science & Engineering
Yu Bin Lee, Eun Mi Kim, Hayeon Byun, Hyung-Kwan Chang, Kwanghee Jeong, Zachary M Aman, Yu Suk Choi, Jungyul Park, Heungsoo Shin
Numerous methods have been reported for the fabrication of 3D multi-cellular spheroids and their use in stem cell culture. Current methods typically relying on the self-assembly of trypsinized, suspended stem cells, however, show limitations with respect to cell viability, throughput, and accurate recapitulation of the natural microenvironment. In this study, we developed a new system for engineering cell spheroids by self-assembly of micro-scale monolayer of stem cells. We prepared synthetic hydrogels with the surface of chemically formed micropatterns (squares/circles with width/diameter of 200 μm) on which mesenchymal stem cells isolated from human nasal turbinate tissue (hTMSCs) were selectively attached and formed a monolayer...
March 1, 2018: Biomaterials
Risa Akizuki, Ryohei Maruhashi, Hiroaki Eguchi, Kazuki Kitabatake, Mitsutoshi Tsukimoto, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Akira Ikari
Chemotherapy resistance is a major problem in the treatment of cancer, but the underlying mechanisms are not fully understood. We found that the expression levels of claudin-1 (CLDN1) and 3, tight junctional proteins, are upregulated in cisplatin (CDDP)-resistant human lung adenocarcinoma A549 (A549R) cells. A549R cells showed cross-resistance to doxorubicin (DXR). Here, the expression mechanism and function of CLDN1 and 3 were examined. CLDN1 and 3 were mainly localized at tight junctions concomitant with zonula occludens (ZO)-1, a scaffolding protein, in A549 and A549R cells...
March 7, 2018: Biochimica et Biophysica Acta
Wadie D Mahauad-Fernandez, Chioma M Okeoma
Bone marrow stromal antigen 2 (BST-2) also known as Tetherin has been implicated in the growth and progression of many cancers. BST-2 employs its pro-tumor effects through the formation of BST-2:BST-2 dimers which ultimately promotes cell to cell and cell to matrix adhesion, cell motility, survival, and growth. The aim of this study was to evaluate the effect of a novel BST-2-based peptide-B49 on adhesion and growth of breast cancer cells. Homotypic/heterotypic adhesion, three-dimensional spheroid formation, and anchorage-independent growth were used to assess the effect of B49 on cell adhesion and growth...
March 9, 2018: Scientific Reports
Klara Janjić, Barbara Cvikl, Christoph Kurzmann, Andreas Moritz, Hermann Agis
BACKGROUND: To understand the responses of the dental pulp to hypoxia is of high relevance for regenerative endodontics and dental traumatology. Here, we aimed to reveal the effects of hypoxia and the hypoxia mimetic agent L-mimosine (L-MIM) on the production of sclerostin (SOST) and dickkopf-1 (DKK-1) in human dental pulp-derived cells (DPC). METHODS: DPC in monolayer, spheroid and tooth slice cultures were treated with L-MIM or hypoxia. Resazurin-based toxicity and MTT assays were performed to determine cell viability...
March 9, 2018: BMC Oral Health
Gang Liu, Wen Xie, Guobing Wei, Yan Yang, Junwei Liu, Tiancai Xu, Weidong Xie, Xiaodong Peng
The hot deformation and dynamic recrystallization behavior of the dual-phase Mg-9Li-3Al-2Sr-2Y alloy had been investigated using a compression test. The typical dual-phase structure was observed, and average of grain size of as-homogenized alloy is about 110 µm. It mainly contains β-Li, α-Mg, Al₄Sr and Al₂Y phases. The dynamic recrystallization (DRX) kinetic was established based on an Avrami type equation. The onset of the DRX process occurred before the peak of the stress-strain flow curves. It shows that the DRX volume fraction increases with increasing deformation temperature or decreasing strain rate...
March 9, 2018: Materials
Marjaana Ojalill, Pekka Rappu, Elina Siljamäki, Pekka Taimen, Peter Boström, Jyrki Heino
BACKGROUND: The composition and organization of extracellular matrix (ECM) are important regulators of cell behavior. In particular in the prostate, this central role of the ECM is further stressed by the fact that several potential markers of prostate stem cells are matrix receptors. METHODS: We established 12 fibroblastic cell lines from cancerous and non-cancerous areas of six prostates and allowed the cells to produce ECM under cell culture conditions. We also performed a proteome wide analysis of the ECM components by mass spectrometry...
March 9, 2018: Prostate
Yeonho Jo, Nakwon Choi, Hong Nam Kim, Jonghoon Choi
In this study, we demonstrate cell culture platforms that can provide a microenvironment similar to in vivo conditions so that in vivo-compatible drug testing results can be obtained from the in vitro experiments. To realize such in vivo microenvironment-mimetic platforms, different culture platforms such as a three-dimensional (3D) cell aggregate film, fluidic environment within a microfluidic system or extracellular matrix (ECM) coating were established. The tumor cell growth rate and sensitivity to doxorubicin (DOX) were studied using the glioblastoma cell line T98G...
March 8, 2018: Artificial Cells, Nanomedicine, and Biotechnology
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