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Xiaolin Lin, Wentao Zhao, Junshuang Jia, Taoyan Lin, Gaofang Xiao, Shengchun Wang, Xia Lin, Yu Liu, Li Chen, Yujuan Qin, Jing Li, Tingting Zhang, Weichao Hao, Bangzhu Chen, Raoying Xie, Yushuang Cheng, Kang Xu, Kaitai Yao, Wenhua Huang, Dong Xiao, Yan Sun
Targeted disruption of Cripto-1 in mice caused embryonic lethality at E7.5, whereas we unexpectedly found that ectopic Cripto-1 expression in mouse embryos also led to embryonic lethality, which prompted us to characterize the causes and mechanisms underlying embryonic death due to ectopic Cripto-1 expression. RCLG/EIIa-Cre embryos displayed complex phenotypes between embryonic day 14.5 (E14.5) and E17.5, including fatal hemorrhages (E14.5-E15.5), embryo resorption (E14.5-E17.5), pale body surface (E14.5-E16...
September 30, 2016: Scientific Reports
M A Ligtenberg, K Witt, F Galvez-Cancino, A Sette, A Lundqvist, A Lladser, R Kiessling
Metastatic melanoma is a fatal disease that responds poorly to classical treatments but can be targeted by T cell-based immunotherapy. Cancer vaccines have the potential to generate long-lasting cytotoxic CD8(+) T cell responses able to eradicate established and disseminated tumors. Vaccination against antigens expressed by tumor cells with enhanced metastatic potential represents a highly attractive strategy to efficiently target deadly metastatic disease. Cripto-1 is frequently over-expressed in human carcinomas and melanomas, but is expressed only at low levels on normal differentiated tissues...
May 2016: Oncoimmunology
Luigi Strizzi, Naira V Margaryan, Pedram Gerami, Zahra Haghighat, Paul W Harms, Gabriele Madonna, Gerardo Botti, Paolo A Ascierto, Mary J C Hendrix
The TGF-β associated growth factor Nodal is highly expressed in aggressive metastatic melanoma. Determining the risk for melanomagenesis from Nodal expression in nevi prior to the development of melanoma may be useful for both the screening and prevention of melanoma. Tissue sections of human adult nevi with or without a history of melanoma were stained by immunohistochemistry (IHC) for Nodal, the Nodal co-receptor Cripto-1, and Notch4, which have previously been shown to be associated with Nodal expression in melanoma...
August 2016: Oncology Letters
Guan Sun, Shu-Shan Yan, Lei Shi, Zheng-Qiang Wan, Nan Jiang, Lin-Shan Fu, Min Li, Jun Guo
Gliomas are the most common type of malignant brain tumor. Studies have identified that miR‑15b is negatively correlated with cripto-1 expression in glioma cells, and these molecules serve an important role in cancer development and progression. The current study was undertaken to further examine the association between these two molecules. Fluorescent quantitative PCR confirmed that miR‑15b expression was significantly downregulated in glioma tissue while cripto‑1 expression was significantly increased...
June 2016: Molecular Medicine Reports
Maria Cristina Rangel, Daniel Bertolette, Nadia P Castro, Malgorzata Klauzinska, Frank Cuttitta, David S Salomon
Cancer has been considered as temporal and spatial aberrations of normal development in tissues. Similarities between mammary embryonic development and cell transformation suggest that the underlying processes required for mammary gland development are also those perturbed during various stages of mammary tumorigenesis and breast cancer (BC) development. The master regulators of embryonic development Cripto-1, Notch/CSL, and Wnt/β-catenin play key roles in modulating mammary gland morphogenesis and cell fate specification in the embryo through fetal mammary stem cells (fMaSC) and in the adult organism particularly within the adult mammary stem cells (aMaSC), which determine mammary progenitor cell lineages that generate the basal/myoepithelial and luminal compartments of the adult mammary gland...
April 2016: Breast Cancer Research and Treatment
Chun Hua Xu, Yan Wang, Li Hua Qian, Li Ke Yu, Xiu Wei Zhang, Qing Bo Wang
INTRODUCTION: Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined. OBJECTIVES: The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC. METHODS: Serum specimens from 592 NSCLC patients, 180 benign lung disease patients, and 240 healthy controls were collected...
November 25, 2015: Clinical Respiratory Journal
Dong-mei Zhang, Yong-Li Bao, Chun-Lei Yu, Yi-meng Wang, Zhen-Bo Song
Cripto-1 is an oncogenic protein belonging to the epidermal growth factor–Cripto-1/FRL-1/Cryptic family. It has important roles in tumor formation and metastasis, but its effects on the immune system are unclear. In the present study, we investigated the effects of Cripto-1 overexpression on macrophage activities and examined the underlying mechanisms. A cell line stably overexpressing Cripto-1 was developed. The culture supernatant from this cell line was collected and used to condition macrophages (RAW264...
February 2016: Immunologic Research
Chun Huang, Wangsheng Chen, Xiaowen Wang, Jinqiu Zhao, Qian Li, Zhongxue Fu
Esophageal carcinoma is a major public health problem worldwide and one of the most aggressively malignant neoplasms. Although considerable diagnostic and therapeutic progress has been made in recent years, the prognosis of EC patients still remains dismal due to high rates of recurrence/metastasis and invasion. Previous studies have demonstrated that Epithelial mesenchymal transition (EMT) is proposed as a critical mechanism for the acquisition of malignant phenotypes by epithelial cells. Several lines of evidence have shown that Cripto-1 plays an important oncogenic role during tumorigenesis by promoting EMT...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
Jia-Hong Wang, Wei Wei, Jing Xu, Zhi-Xing Guo, Cheng-Zuo Xiao, Yong-Fa Zhang, Pei-En Jian, Xiao-Liang Wu, Ming Shi, Rong-Ping Guo
Cripto-1 could promote tumorigenesis in a wide range of carcinomas, yet little is known in hepatocellular carcinoma (HCC). The expression of Cripto-1 and MMP-9 were assessed by immunohistochemistry in 205 HCC specimens. The correlation between Cripto-1 and MMP-9, clinicopathological/prognostic value in HCC was examined. Cripto-1 overexpression was correlated with larger tumor, TNM stage, BCLC stage and tumor recurrence. In multivariate analyses, Cripto-1 was an independent predictor for overall survival (OS) and time to recurrence (TTR)...
October 27, 2015: Oncotarget
Annalia Focà, Luca Sanguigno, Giuseppina Focà, Luigi Strizzi, Roberta Iannitti, Rosanna Palumbo, Mary J C Hendrix, Antonio Leonardi, Menotti Ruvo, Annamaria Sandomenico
Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling...
2015: International Journal of Molecular Sciences
F Francescangeli, P Contavalli, M L De Angelis, M Baiocchi, G Gambara, A Pagliuca, A Fiorenzano, C Prezioso, A Boe, M Todaro, G Stassi, N P Castro, K Watanabe, D S Salomon, R De Maria, G Minchiotti, A Zeuner
Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level...
October 2015: Cell Death and Differentiation
Malgorzata Klauzinska, Daniel Bertolette, Sudhamsh Tippireddy, Luigi Strizzi, Peter C Gray, Monica Gonzales, Meg Duroux, Menotti Ruvo, Christian Wechselberger, Nadia P Castro, Maria Cristina Rangel, Annalia Focà, Annamaria Sandomenico, Mary J C Hendrix, David Salomon, Frank Cuttitta
Cripto-1 (CR-1) is a multifunctional embryonic protein that is re-expressed during inflammation, wound repair, and malignant transformation. CR-1 can function either as a tethered co-receptor or shed as a free ligand underpinning its flexible role in cell physiology. CR-1 has been shown to mediate cell growth, migration, invasion, and induce epithelial to mesenchymal transition (EMT). The main signaling pathways mediating CR-1 effects include Nodal-dependent (Smad2/3) and Nodal-independent (Src/p44/42/Akt) signaling transduction pathways...
2015: Connective Tissue Research
Nadia P Castro, David S Salomon
No abstract text is available yet for this article.
August 2015: Aging
Chun-Hua Xu, Lan Cao, Ying Wei, Li-Ke Yu
BACKGROUND: Cripto-1 (CR-1) plays an important role in angiogenesis related to tumor growth, in concert with vascular endothelial growth factor (VEGF), and enhanced expression of CR-1 has been reported in lung cancer tissue. METHODS: Patients with lung cancer (n = 156) and healthy volunteers (n = 60) were enrolled in the study. Serum CR-1 and VEGF concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: Patients with lung cancer had higher serum CR-1 (4...
October 2015: International Journal of Biological Markers
Nadia P Castro, Natalie D Fedorova-Abrams, Anand S Merchant, Maria Cristina Rangel, Tadahiro Nagaoka, Hideaki Karasawa, Malgorzata Klauzinska, Stephen M Hewitt, Kajal Biswas, Shyam K Sharan, David S Salomon
Triple-negative breast cancer (TNBC) presents the poorest prognosis among the breast cancer subtypes and no current standard therapy. Here, we performed an in-depth molecular analysis of a mouse model that establishes spontaneous lung metastasis from JygMC(A) cells. These primary tumors resembled the triple-negative breast cancer (TNBC) both phenotypically and molecularly. Morphologically, primary tumors presented both epithelial and spindle-like cells but displayed only adenocarcinoma-like features in lung parenchyma...
May 20, 2015: Oncotarget
Vijaya S Pilli, K Gupta, Bhanu P Kotha, Gopala Krishna Aradhyam
Transcription factor Snail mediates epithelial to mesenchymal transitions (EMT) by coordinate repression of epithelial markers, facilitating mass cell movement during germ layer formation. Aberrant reprogramming in its signaling pathways causes metastatic cancer. Snail's involvement in "fate-changing" decisions is however not understood. Cripto-1 shares a common temporal expression pattern with Snail during development. While Cripto-1 is required for mammary morphogenesis and hematopoietic stem cell renewal, its unregulated expression causes metastatic cancers...
May 8, 2015: FEBS Letters
Yangyang Shan, Shenglei Li
To research the expression in human lung adenocarcinoma tissue of Cripto-1 (teratocarcinoma derived growth factor-1) gene protein and Activin-A gene protein, and explore the relationship and clinical significance between the two gene protein and clinical pathological characteristic of lung adenocarcinoma. This study had applied the immunohistochemical method to detect the 188 cases of lung adenocarcinoma and expression of Cripto-1 protein and Activin-A protein in 100 cases of normal lung tissue. Then, analysis the relationship between these two-gene protein and clinical lung adenocarcinoma histopathological features, and inherent correlation between these two genes...
March 2015: Pakistan Journal of Pharmaceutical Sciences
Hee Yeon Lee, Ji-Han Jung, Hyun-Min Cho, Sung Hwan Kim, Kang-Moon Lee, Hyung-Jin Kim, Jong Hoon Lee, Byoung Yong Shim
PURPOSE: We investigated the relationships between biomarkers related to endoplasmic reticulum stress proteins (glucose-regulated protein of molecular mass 78 [GRP78] and Cripto-1 [teratocarcinoma-derived growth factor 1 protein]), pathologic response, and prognosis in locally advanced rectal cancer. MATERIALS AND METHODS: All clinical stage II and III rectal cancer patients received 50.4 Gy over 5.5 weeks, plus 5-fluorouracil (400 mg/m(2)/day) and leucovorin (20 mg/m(2)/day) bolus on days 1 to 5 and 29 to 33, and surgery was performed at 7 to 10 weeks after completion of all therapies...
October 2015: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Pojul Loying, Janvie Manhas, Sudip Sen, Biplab Bose
Cripto-1 (CR-1) is involved in various processes in embryonic development and cancer. Multiple pathways regulate CR-1 expression. Our present work demonstrates a possible positive feedback circuit where CR-1 induces its own expression. Using U-87 MG cells treated with exogenous CR-1, we show that such induction involves ALK4/SMAD2/3 pathway. Stochasticity in gene expression gives rise to heterogeneity in expression in genetically identical cells. Positive feedback increases such heterogeneity and often gives rise to two subpopulations of cells, having higher and lower expression of a gene...
2015: PloS One
Daniela Ruggiero, Stefania Nappo, Teresa Nutile, Rossella Sorice, Francesco Talotta, Emilia Giorgio, Celine Bellenguez, Anne-Louise Leutenegger, Giovanna L Liguori, Marina Ciullo
Cripto, the founding member of the EGF-CFC genes, plays an essential role in embryo development and is involved in cancer progression. Cripto is a GPI-anchored protein that can interact with various components of multiple signaling pathways, such as TGF-β, Wnt and MAPK, driving different processes, among them epithelial-mesenchymal transition, cell proliferation, and stem cell renewal. Cripto protein can also be cleaved and released outside the cell in a soluble and still active form. Cripto is not significantly expressed in adult somatic tissues and its re-expression has been observed associated to pathological conditions, mainly cancer...
January 2015: PLoS Genetics
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