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Volodymyr Porokh, Petr Vaňhara, Tomas Bárta, Lucie Jurečková, Dáša Bohačiaková, Veronika Pospíšilová, Daniela Mináriková, Zuzana Holubcová, Vendula Pelková, Karel Souček, Ales Hampl
Chromosomal instability evoked by abnormalities in centrosome numbers has been traditionally considered as a hallmark of aberrant, typically cancerous or senescent cells. We have reported previously that pristine human embryonic stem cells (hESC) suffer from high frequency of supernumerary centrosomes and hence may be prone to undergo abnormal mitotic divisions. We have also unraveled that this phenomenon of multicentrosomal mitoses vanishes with prolonged time in culture and with initiation of differentiation, and it is strongly affected by the culture substratum...
June 8, 2018: Stem Cells and Development
YingYu Zhang, XuGuang Mi, ZhenBo Song, YuXin Li, YingShi, JunQi Niu
Cripto-1 is an oncogenic protein that belongs to the epidermal growth factor (EGF)-cripto-1/FRL1/cryptic (CFC) family. It has been shown to stimulate tumorigenesis and metastasis by promoting cancer cell proliferation, epithelial-to-mesenchymal transition (EMT), and tumor angiogenesis. However, the role of Cripto-1 in cell survival and apoptosis remains largely undefined. In the present study, we found that Cripto-1 is significantly upregulated in a number of human cancer cell lines. The membrane-associated but not the soluble form of Cripto-1 promotes resistance to drug-induced caspase-3 cleavage, an indicator of apoptosis...
May 25, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Vahid Bagheri, Bahram Memar, Ramezan Behzadi, Mohsen Aliakbarian, Ali Jangjoo, Mostafa Mehrabi Bahar, Samaneh Talebi, Mehran Gholamin, Mohammad R Abbaszadegan
Gastric cancer (GC) is the third and fifth cause of cancer-associated mortality for men and women throughout the world, respectively. Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Cancer stem cells (CSCs) due to their pivotal role in tumor initiation, growth, progression, invasion, distant metastasis, recurrence and resistance to anticancer drugs are very appealing targets for cancer therapies. Here, we isolated and identified CSCs from a chemotherapy-treated patient...
May 10, 2018: Journal of Cellular Physiology
S Kim, Y M Yoon, Y-S Han, J H Lee, J Hur, S H Lee
OBJECTIVES: The purpose of this study was to explore the effectiveness of concurrent GRP78 overexpression combined with Cripto on hMSC proliferation and migration both in vitro and in vivo. Specifically, we explored whether the treatment enhances effectiveness of hMSC transplantation in ischaemic tissue. MATERIALS AND METHODS: Human MSCs obtained from human adipose tissue were cultured in α-minimum essential medium (Hyclone, Logan, UT, USA) supplemented with 10% (v/v) foetal bovine serum (Hyclone), 100 U mL-1 penicillin and 100 μg mL-1 streptomycin...
May 2, 2018: Cell Proliferation
Shupei Qiao, Yi Liu, Fengtong Han, Mian Guo, Xiaolu Hou, Kangruo Ye, Shuai Deng, Yijun Shen, Yufang Zhao, Haiying Wei, Bing Song, Lifen Yao, Weiming Tian
Transplanted stem cells constitute a new therapeutic strategy for the treatment of neurological disorders. Emerging evidence indicates that a negative microenvironment, particularly one characterized by the acute inflammation/immune response caused by physical injuries or transplanted stem cells, severely impacts the survival of transplanted stem cells. In this study, to avoid the influence of the increased inflammation following physical injuries, an intelligent, double-layer, alginate hydrogel system is designed...
May 2, 2018: Advanced Healthcare Materials
Sofia Karkampouna, Danny van der Helm, Peter C Gray, Lanpeng Chen, Irena Klima, Joël Grosjean, Mark C Burgmans, Arantza Farina-Sarasqueta, Ewa B Snaar-Jagalska, Deborah M Stroka, Luigi Terracciano, Bart van Hoek, Alexander F Schaapherder, Susan Osanto, George N Thalmann, Hein W Verspaget, Minneke J Coenraad, Marianna Kruithof-de Julio
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite increasing treatment options for this disease, prognosis remains poor. CRIPTO (TDGF1) protein is expressed at high levels in several human tumours and promotes oncogenic phenotype. Its expression has been correlated to poor prognosis in HCC. In this study, we aimed to elucidate the basis for the effects of CRIPTO in HCC. We investigated CRIPTO expression levels in three cohorts of clinical cirrhotic and HCC specimens...
March 31, 2018: Journal of Pathology
Leorik Pereira Silva, Luiz Arthur Barbosa da Silva, Bruno Tavares Sedassari, Suzana Cantanhede Orsini Machado de Sousa, Joabe Dos Santos Pereira, Lélia Batista de Souza, Márcia Cristina da Costa Miguel
INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique...
June 2018: European Archives of Oto-rhino-laryngology
Chun Hua Xu, Chuan Zhen Chi, Qian Zhang, Yu Chao Wang, Wei Wang, Qi Yuan, Ping Zhan, Xiu Wei Zhang, Yong Lin
INTRODUCTION: Cripto-1 (CR-1) is a member of the epidermal growth factor (EGF)-CFC protein family, which is involved in tumor pathogenesis. OBJECTIVES: This study aimed to explore the diagnostic and prognostic value of serum CR-1 level in patients with non-small cell lung cancer (NSCLC). METHOD: Serum specimens from 312 NSCLC patients and 120 healthy controls were collected. Serum CR-1 level was measured using enzyme-linked immunosorbent assay (ELISA)...
March 23, 2018: Clinical Respiratory Journal
Eran Gershon, Ron Hadas, Michal Elbaz, Evan Booker, Moran Muchnik, Alona Kleinjan-Elazary, Sharon Karasenti, Olga Genin, Yuval Cinnamon, Peter C Gray
Cripto-1 (TDGF1) is a multifunctional signaling factor that stimulates cellular effects, including proliferation, migration, survival, epithelial-to-mesenchymal transition, and angiogenesis, to regulate embryogenesis, tissue homeostasis, and tumorigenesis. Those cell behaviors are also associated with implantation of the embryo into the uterine wall, and this led us to investigate the role of embryo-derived Cripto in embryo attachment and implantation. In this study, we show that Cripto and its signaling mediator GRP78 are uniquely localized to embryo implantation sites...
April 1, 2018: Endocrinology
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
Kang-Seo Park, Yong Wha Moon, Mark Raffeld, Dae Ho Lee, Yisong Wang, Giuseppe Giaccone
OBJECTIVES: Cripto-1 (CR-1) plays a critical role in the activation of SMAD, SRC, and epithelial-to-mesenchymal transition (EMT) pathways and has been shown to be prognostic in several cancer types. In addition, we showed that CR-1 renders EGFR-mutated NSCLC cells resistant to EGFR-TKI through the activation of SRC and EMT via miR-205 downregulation. This study aimed to investigate the correlation between expression of CR-1 and miR-205 and prognosis of NSCLC patients with or without EGFR mutations...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Maha A Qadan, Nicolas S Piuzzi, Cynthia Boehm, Wesley Bova, Malcolm Moos, Ronald J Midura, Vincent C Hascall, Christopher Malcuit, George F Muschler
BACKGROUND AIMS: Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT)...
March 2018: Cytotherapy
Ding Wu, Zhan Shi, Hao Xu, Renfu Chen, Song Xue, Xiaoqing Sun
Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto-1/FRL1/Cryptic gene family that plays a key role in the various malignant cancers. However, the role of CR-1 in prostate carcinoma (PCa) remains limited. The expression of CR-1 was down-regulated by small interfering RNA (siRNA). Western blot measured the expression levels of CR-1 and some related proteins. We performed Cell Counting Kit-8, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and flow cytometry to detect the cellular proliferation and cycle...
September 2017: Journal of Biosciences
Maria Grazia Perino, Satoshi Yamanaka, Daniel R Riordon, Yelena Tarasova, Kenneth R Boheler
Numerous groups have documented that Ascorbic Acid (AA) promotes cardiomyocyte differentiation from both mouse and human ESCs and iPSCs. AA is now considered indispensable for the routine production of hPSC-cardiomyocytes (CMs) using defined media; however, the mechanisms involved with the inductive process are poorly understood. Using a genetically modified mouse embryonic stem cell (mESC) line containing a dsRED transgene driven by the cardiac-restricted portion of the ncx1 promoter, we show that AA promoted differentiation of mESCs to CMs in a dose- and time-dependent manner...
2017: PloS One
Valentina L Kouznetsova, Hannah Hu, Knut Teigen, Maurizio Zanetti, Igor F Tsigelny
The ER resident chaperone molecule GRP78 has been shown to translocate to the cell surface where it associates with Cripto and signals cell growth, playing a still partially understood role in tumorigenesis. Consequently, a better understanding of GRP78 topology and structure at the surface of cancer cells represents an important step in the development of a new class of therapeutics. Here, we used a set of programs for creation of a complex containing GRP78 and Cripto proteins. We elucidated possible interactions of GRP78, Cripto, and their complex with the membrane...
March 2018: Protein Science: a Publication of the Protein Society
Luisa Calvanese, Annalia Focà, Annamaria Sandomenico, Giuseppina Focà, Andrea Caporale, Nunzianna Doti, Emanuela Iaccarino, Antonio Leonardi, Gabriella D'Auria, Menotti Ruvo, Lucia Falcigno
Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1). By STD-NMR technique, we investigated the interaction of Nodal fragments with 3D1 with the aim to elucidate at atomic level the interaction surface...
December 15, 2017: Bioorganic & Medicinal Chemistry
Hua Zhang, Bin Zhang, Liuwei Gao, Lianmin Zhang, Kaikai Zhu, Runfen Cheng, Changli Wang
Cripto-1 can promote tumourigenesis and may be a potential prognostic biomarker in several malignancies, yet little is known about this protein in lung adenocarcinoma (LAC). The aim of this study was to evaluate the prognostic value of cripto-1 expression in a cohort of patients with LAC. Tumours from 290 patients with pathologically confirmed LAC were used for an immunohistochemical analysis of cripto-1 expression. The correlation between cripto-1 expression and the clinicopathological parameters of patients, EGFR-TKI sensitivity was analysed...
October 3, 2017: Oncotarget
SeungPil Yun, Chul Won Yun, Jun Hee Lee, SangMin Kim, Sang Hun Lee
Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1...
August 25, 2017: Biomolecules & Therapeutics
Aparna Kalyan, Benedito A Carneiro, Sunandana Chandra, Jason Kaplan, Young Kwang Chae, Maria Matsangou, Mary J C Hendrix, Francis Giles
The tumor microenvironment is a vital feature of oncogenesis and tumor progression. There are several parallels between cancer cells and early developmental stem cells, including their plasticity and signaling mechanisms. In early fetal development, Nodal is expressed for endodermal and mesodermal differentiation. This expression has been shown reemerge in the setting of epithelial cancers, such as breast and melanoma. High Nodal expression correlates to an aggressive tumor grade in these malignancies. Nodal signal begins with its interaction with its coreceptor, Cripto-1, leading to activation of Smad2/Smad3 and ultimately downstream transcription and translation...
May 2017: Molecular Cancer Therapeutics
Q Q Xu, C C Ren, L Yang, Z Y Ban, L Liu, J H Lu, Y X Yu
No abstract text is available yet for this article.
May 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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