scholarly journals Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 439 ◽  
Author(s):  
Dusan Hrckulak ◽  
Lucie Janeckova ◽  
Lucie Lanikova ◽  
Vitezslav Kriz ◽  
Monika Horazna ◽  
...  
Keyword(s):  
T Cell ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Human Cancer ◽  
Wnt Signaling Pathway ◽  
Human Cells ◽  
Cellular Systems ◽  
Mouse Tissue ◽  
T Cell Factor ◽  
Human Cancer Cells

T-cell factor 4 (TCF4), together with β-catenin coactivator, functions as the major transcriptional mediator of the canonical wingless/integrated (Wnt) signaling pathway in the intestinal epithelium. The pathway activity is essential for both intestinal homeostasis and tumorigenesis. To date, several mouse models and cellular systems have been used to analyze TCF4 function. However, some findings were conflicting, especially those that were related to the defects observed in the mouse gastrointestinal tract after Tcf4 gene deletion, or to a potential tumor suppressive role of the gene in intestinal cancer cells or tumors. Here, we present the results obtained using a newly generated conditional Tcf4 allele that allows inactivation of all potential Tcf4 isoforms in the mouse tissue or small intestinal and colon organoids. We also employed the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system to disrupt the TCF4 gene in human cells. We showed that in adult mice, epithelial expression of Tcf4 is indispensable for cell proliferation and tumor initiation. However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors.

Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation

2004 ◽  
Vol 113 (3) ◽  
pp. 261-269 ◽  
Author(s):  
Shigeo Koido ◽  
Masaya Ohana ◽  
Chunlei Liu ◽  
Najmosama Nikrui ◽  
John Durfee ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Human Cancer ◽  
Antigen Expression ◽  
Cell Stimulation ◽  
Human Cancer Cells ◽  
T Cell Stimulation

scholarly journals GRG5/AES Interacts with T-Cell Factor 4 (TCF4) and Downregulates Wnt Signaling in Human Cells and Zebrafish Embryos

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e67694 ◽  
Author(s):  
Ângela M. Sousa Costa ◽  
Isabel Pereira-Castro ◽  
Elisabete Ricardo ◽  
Forrest Spencer ◽  
Shannon Fisher ◽  
...  
Keyword(s):  
T Cell ◽  
Wnt Signaling ◽  
Human Cells ◽  
Zebrafish Embryos ◽  
T Cell Factor

scholarly journals A Novel and Efficient Approach for Screening Cancer Cell Specific Monoclonal Antibodies

2019 ◽  
Author(s):  
Xin-Hui Pei
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Liver ◽  
Human Cancer ◽  
Human Cells ◽  
Specific Antibodies ◽  
Human Cancer Cells ◽  
Normal Human ◽  
Normal Human Cells

AbstractCancer cell specific antibodies are pivotal tools in developing new immunotherapies for treating cancers. However, acquirement of cancer cell specific antibodies is time-consuming and often arduous. To circumvent such a barrier, we developed a novel antibody-screening method that can be used to efficiently produce cancer cell specific antibodies by an ‘antibody filter’ mechanism. First, we used normal human cells to perform the immunization in mice and collected the antisera. Second, we used human cancer cells together with the antisera against normal human cells to immunize another batch of mice. Theoretically, the antisera were able to neutralize the antigens from normal human cells, and therefore specific antigens only expressed in cancer cells could take advantage of the immunization. Third, we screened positive clones that are specific for cancer cells but not normal cells. Using this conceptual method, we successfully obtained 11 monoclonal antibodies that are specific for a human liver cancer cells line (HepG2) but not for a normal human liver cell line (HH). In addition, these clones failed to recognize other human cancer cells originated from different tissues, further highlighting the specificity. Collectively, we provide a novel and effective approach for screening cancer cell specific monoclonal antibodies, which may significantly facilitate the development of new anti-cancer therapeutics.

Isocarbostyril Alkaloids and their Derivatives as Promising Antitumor Agents

2013 ◽  
Vol 411-414 ◽  
pp. 3150-3153
Author(s):  
Yu Bin Ji ◽  
Jia Zheng ◽  
Ning Chen ◽  
Dong Xue Song ◽  
Yan Dong ◽  
...  
Keyword(s):  
Cancer Cells ◽  
High Efficiency ◽  
Antitumor Agents ◽  
Human Cancer ◽  
Hot Spot ◽  
Human Cells ◽  
Human Cancer Cells ◽  
Basic Nitrogen ◽  
Normal Human ◽  
Low Toxicity

socarbostyril alkaloids is a kind of alkaloid does not contain basic nitrogen atoms and is represented by hydroxylated benzophenanthridone or isoquinolinone types of structure. The most widely known compounds of this group are narciclasine, lycoricidine , and pancratistatin. They have demonstrated to inhibite the proliferation of many human cancer cells, and at the same time have no affect on normal human cells under a certain dose, they have a high efficiency and low toxicity in antitumor area. Now this kind of compound has been a hot spot research to antitumor workers. The present paper reviews the origin and the antitumor function of the Isocarbostyril alkaloids.

scholarly journals Transfer of the Interleukin-2 Gene Into Human Cancer Cells Induces Specific Antitumor Recognition and Restores the Expression of CD3/T-Cell Receptor Associated Signal Transduction Molecules

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 212-218 ◽  
Author(s):  
Anna Guarini ◽  
Ludovica Riera ◽  
Alessandro Cignetti ◽  
Laura Montacchini ◽  
Massimo Massaia ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Cancer Cells ◽  
Tyrosine Kinases ◽  
Human Cancer ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Gm Csf ◽  
Human Cancer Cells ◽  
Tnf Α

Abstract Normal peripheral blood mononuclear cells (PBMC) were cocultured with a human lung cancer cell line (LC89) transduced with the interleukin-2 (IL-2), IL-7, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and tumor necrosis factor-α (TNF-α) genes to evaluate the capacity of the engineered cells to: allow survival of CD3+ and CD56+ cells, generate cytotoxic effectors with HLA class I restricted and unrestricted antitumor activity, and interfere in the molecular organization of the CD3/T-cell receptor associated signal transduction machinery. When PBMC were cultured up to 3 weeks with IL-2 releasing LC89 cells (LC89/IL-2), the number of viable CD3+ and CD56+ lymphocytes was much greater than in cultures with parental cells or with LC89 cells transduced with the other cytokine genes. After 1 week of coculture, a variable degree of restricted and unrestricted killing directed against different targets was observed. When the cultures were prolonged up to 3 weeks, LC89/IL-2 cells induced a marked increase in specific cytotoxic activity, which was coupled to a further enhancement of unrestricted lytic function. In the presence of LC89/IL-7 cells the degree of specific lysis remained unchanged, whereas unrestricted effectors were markedly decreased. No cytotoxic activity could be induced by LC89/GM-CSF and LC89/TNF-α cells in the few lymphocytes surviving after 3 weeks of culture. Coculture of parental LC89 cells with PBMC was consistently associated with a downmodulation in the expression of the CD3 ζ chain, as well as of the tyrosine kinases p56lck and ZAP-70. On the contrary, LC89/IL-2 cells, and not LC89 cells transduced with the IL-7, GM-CSF, or TNF-α gene, were capable of reverting the immunosuppressive effect exerted by the tumor cells. This protective effect could be maintained in cultures prolonged up to 4 weeks. When the same cultures were set up in Transwell, ie, with a membrane separation between cancer cells and PBMC, the expression of the CD3 ζ chain and of the p56lck and ZAP-70 tyrosine kinases remained unchanged under all culture conditions, indicating that the downmodulation of T-cell signal transduction molecules requires a direct cell to cell contact. These results show that transfer of the IL-2 gene into the DNA of human cancer cells promotes both restricted and unrestricted antitumor activity, and is capable of restoring and maintaining the expression of molecules involved in the process of T-cell mediated tumor cell recognition, thus underlining the potential role of the IL-2 gene in the design of vaccination protocols with cytokine gene transduced cancer cells.

scholarly journals SOMATIC CELL HYBRIDS BETWEEN MOUSE PERITONEAL MACROPHAGES AND SV40-TRANSFORMED HUMAN CELLS

1974 ◽  
Vol 140 (5) ◽  
pp. 1221-1229 ◽  
Author(s):  
Carlo M. Croce ◽  
Hilary Koprowski
Keyword(s):  
Somatic Cell ◽  
Cancer Cells ◽  
Human Cancer ◽  
Peritoneal Macrophages ◽  
Human Cells ◽  
Somatic Cell Hybrids ◽  
Human Cancer Cells ◽  
Cell Hybrids ◽  
Hypoxanthine Guanine Phosphoribosyltransferase ◽  
Mouse Peritoneal Macrophages

Fusion of mouse peritoneal macrophages with SV40-transformed human cells, deficient in hypoxanthine guanine phosphoribosyltransferase, resulted in the formation of transformed somatic cell hybrids which contained, without exception, the human chromosome 7 carrying the SV40 genome. It is postulated that the hybridization of mouse nondividing cells with human cancer cells could permit the identification of the human "oncogenic" chromosome(s) present in human cancer cells, since such chromosome(s) should be retained by the totality of the mouse-human hybrid cells.

Fucoidin enhances dendritic cell-mediated T-cell cytotoxicity against NY-ESO-1 expressing human cancer cells

2010 ◽  
Vol 392 (3) ◽  
pp. 329-334 ◽  
Author(s):  
Yaling Hu ◽  
Samuel Chak-Sum Cheng ◽  
Kin-Tak Chan ◽  
Yan Ke ◽  
Bofu Xue ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Cancer Cells ◽  
Human Cancer ◽  
Cell Cytotoxicity ◽  
Human Cancer Cells ◽  
T Cell Cytotoxicity

scholarly journals Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein

2001 ◽  
Vol 21 (1) ◽  
pp. 330-342 ◽  
Author(s):  
Shin-ichiro Hino ◽  
Shosei Kishida ◽  
Tatsuo Michiue ◽  
Akimasa Fukui ◽  
Ikuo Sakamoto ◽  
...  
Keyword(s):  
T Cell ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Mammalian Cells ◽  
Pdz Domain ◽  
Wnt Signaling Pathway ◽  
Negative Regulator ◽  
T Cell Factor ◽  
Novel Protein ◽  
Inducible Gene

ABSTRACT In attempting to clarify the roles of Dvl in the Wnt signaling pathway, we identified a novel protein which binds to the PDZ domain of Dvl and named it Idax (for inhibition of the Dvl and Axin complex). Idax and Axin competed with each other for the binding to Dvl. Immunocytochemical analyses showed that Idax was localized to the same place as Dvl in cells and that expression of Axin inhibited the colocalization of Dvl and Idax. Further, Wnt-induced accumulation of β-catenin and activation of T-cell factor in mammalian cells were suppressed by expression of Idax. Expression of Idax inXenopus embryos induced ventralization with a reduction in the expression of siamois, a Wnt-inducible gene. Idax inhibited Wnt- and Dvl- but not β-catenin-induced axis duplication. It is known that Dvl is a positive regulator in the Wnt signaling pathway and that the PDZ domain is important for this activity. Therefore, these results suggest that Idax functions as a negative regulator of the Wnt signaling pathway by directly binding to the PDZ domain of Dvl.

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