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 Secretoglobin 3A2 eliminates human cancer cells through pyroptosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shigetoshi Yokoyama ◽  
Shun Nakayama ◽  
Lei Xu ◽  
Aprile L. Pilon ◽  
Shioko Kimura
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Human Cancer Cells

AbstractNon-canonical inflammasome activation that recognizes intracellular lipopolysaccharide (LPS) causes pyroptosis, the inflammatory death of innate immune cells. The role of pyroptosis in innate immune cells is to rapidly eliminate pathogen-infected cells and limit the replication niche in the host body. Whether this rapid cell elimination process of pyroptosis plays a role in elimination of cancer cells is largely unknown. Our earlier study demonstrated that a multi-functional secreted protein, secretoglobin (SCGB) 3A2, chaperones LPS to cytosol, and activates caspase-11 and the non-canonical inflammasome pathway, leading to pyroptosis. Here we show that SCGB3A2 exhibits marked anti-cancer activity against 5 out of 11 of human non-small cell lung cancer cell lines in mouse xenographs, while no effect was observed in 6 of 6 small cell lung cancer cell lines examined. All SCGB3A2-LPS-sensitive cells express syndecan 1 (SDC1), a SCGB3A2 cell surface receptor, and caspase-4 (CASP4), a critical component of the non-canonical inflammasome pathway. Two epithelial-derived colon cancer cell lines expressing SDC1 and CASP4 were also susceptible to SCGB3A2-LPS treatment. TCGA analysis revealed that lung adenocarcinoma patients with higher SCGB3A2 mRNA levels exhibited better survival. These data suggest that SCGB3A2 uses the machinery of pyroptosis for the elimination of human cancer cells via the non-canonical inflammasome pathway, and that SCGB3A2 may serve as a novel therapeutic to treat cancer, perhaps in combination with immuno and/or targeted therapies.

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.

scholarly journals Chimeric antigen receptors that trigger phagocytosis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Meghan A Morrissey ◽  
Adam P Williamson ◽  
Adriana M Steinbach ◽  
Edward W Roberts ◽  
Nadja Kern ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cell ◽  
Human Cancer ◽  
Antibody Fragment ◽  
Cell Number ◽  
Antigen Receptors ◽  
Chimeric Antigen Receptors ◽  
Cell Therapies ◽  
Human Cancer Cells

Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T cells to kill cancer. The success of CAR-T cell therapies highlights the promise of programmed immunity and suggests that applying CAR strategies to other immune cell lineages may be beneficial. Here, we engineered a family of Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that direct macrophages to engulf specific targets, including cancer cells. CAR-Ps consist of an extracellular antibody fragment, which can be modified to direct CAR-P activity towards specific antigens. By screening a panel of engulfment receptor intracellular domains, we found that the cytosolic domains from Megf10 and FcRɣ robustly triggered engulfment independently of their native extracellular domain. We show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole human cancer cells. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. Finally, we show that CAR-P expressing murine macrophages reduce cancer cell number in co-culture by over 40%.

scholarly journals Arginine Methylation Regulates Telomere Length and Stability

2009 ◽  
Vol 29 (18) ◽  
pp. 4918-4934 ◽  
Author(s):  
Taylor R. H. Mitchell ◽  
Kimberly Glenfield ◽  
Kajaparan Jeyanthan ◽  
Xu-Dong Zhu
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Telomere Length ◽  
Control Cell ◽  
Arginine Methylation ◽  
Human Cells ◽  
Focus Formation ◽  
Basic Domain ◽  
Normal Human ◽  
Normal Human Cells

ABSTRACT TRF2, a component of the shelterin complex, functions to protect telomeres. TRF2 contains an N-terminal basic domain rich in glycines and arginines, similar to the GAR motif that is methylated by protein arginine methyltransferases. However, whether arginine methylation regulates TRF2 function has not been determined. Here we report that amino acid substitutions of arginines with lysines in the basic domain of TRF2 induce telomere dysfunction-induced focus formation, leading to induction of cellular senescence. We have demonstrated that cells overexpressing TRF2 lysine mutants accumulate telomere doublets, indicative of telomere instability. We uncovered that TRF2 interacts with PRMT1, and its arginines in the basic domain undergo PRMT1-mediated methylation both in vitro and in vivo. We have shown that loss of PRMT1 induces growth arrest in normal human cells but has no effect on cell proliferation in cancer cells, suggesting that PRMT1 may control cell proliferation in a cell type-specific manner. We found that depletion of PRMT1 in normal human cells results in accumulation of telomere doublets, indistinguishable from overexpression of TRF2 lysine mutants. PRMT1 knockdown in cancer cells upregulates TRF2 association with telomeres, promoting telomere shortening. Taken together, these results suggest that PRMT1 may control telomere length and stability in part through TRF2 methylation.

Anti-neoplastic agent thymoquinone induces degradation of α and β tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts

2011 ◽  
Vol 30 (5) ◽  
pp. 1813-1819 ◽  
Author(s):  
Mahmoud Alhosin ◽  
Abdulkhaleg Ibrahim ◽  
Abdelaziz Boukhari ◽  
Tanveer Sharif ◽  
Jean-Pierre Gies ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Human Fibroblasts ◽  
Human Cancer Cells ◽  
Normal Human ◽  
Β Tubulin

scholarly journals Deficiency of Ku Induces Host Cell Exploitation in Human Cancer Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Okay Saydam ◽  
Nurten Saydam
Keyword(s):  
Host Cell ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Human Cancer ◽  
Therapy Resistance ◽  
Host Cells ◽  
Human Cancer Cells ◽  
Parasitic Lifestyle

Cancer metastasis is the major cause of death from cancer (Massague and Obenauf, 2016; Steeg, 2016). The extensive genetic heterogeneity and cellular plasticity of metastatic tumors set a prime barrier for the current cancer treatment protocols (Boumahdi and de Sauvage, 2020). In addition, acquired therapy resistance has become an insurmountable obstacle that abolishes the beneficial effects of numerous anti-cancer regimens (De Angelis et al., 2019; Boumahdi and de Sauvage, 2020). Here we report that deficiency of Ku leads to the exploitation of host cells in human cancer cell line models. We found that, upon conditional deletion of XRCC6 that codes for Ku70, HCT116 human colorectal cancer cells gain a parasitic lifestyle that is characterized by the continuous cycle of host cell exploitation. We also found that DAOY cells, a human medulloblastoma cell line, innately lack nuclear Ku70/Ku86 proteins and utilize the host-cell invasion/exit mechanism for maintenance of their survival, similarly to the Ku70 conditionally-null HCT116 cells. Our study demonstrates that a functional loss of Ku protein promotes an adaptive, opportunistic switch to a parasitic lifestyle in human cancer cells, providing evidence for a previously unknown mechanism of cell survival in response to severe genomic stress. We anticipate that our study will bring a new perspective for understanding the mechanisms of cancer cell evolution, leading to a shift in the current concepts of cancer therapy protocols directed to the prevention of cancer metastasis and therapy resistance.

scholarly journals System-Wide Analysis of Protein Acetylation and Ubiquitination Reveals a Diversified Regulation in Human Cancer Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 411 ◽  
Author(s):  
Hiroko Kozuka-Hata ◽  
Aya Kitamura ◽  
Tomoko Hiroki ◽  
Aiko Aizawa ◽  
Kouhei Tsumoto ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Translational Control ◽  
Large Scale ◽  
Human Cancer ◽  
Initiation Factor ◽  
Protein Acetylation ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Lysine Modification

Post-translational modifications are known to be widely involved in the regulation of various biological processes, through the extensive diversification of each protein function at the cellular network level. In order to unveil the system-wide function of the protein lysine modification in cancer cell signaling, we performed global acetylation and ubiquitination proteome analyses of human cancer cells, based on high-resolution nanoflow liquid chromatography–tandem mass spectrometry, in combination with the efficient biochemical enrichment of target modified peptides. Our large-scale proteomic analysis enabled us to identify more than 5000 kinds of ubiquitinated sites and 1600 kinds of acetylated sites, from representative human cancer cell lines, leading to the identification of approximately 900 novel lysine modification sites in total. Very interestingly, 236 lysine residues derived from 141 proteins were found to be modified with both ubiquitination and acetylation. As a consequence of the subsequent motif extraction analyses, glutamic acid (E) was found to be highly enriched at the position (−1) for the lysine acetylation sites, whereas the same amino acid was relatively dispersed along the neighboring residues of the lysine ubiquitination sites. Our pathway analysis also indicated that the protein translational control pathways, such as the eukaryotic initiation factor 2 (EIF2) and the ubiquitin signaling pathways, were highly enriched in both of the acetylation and ubiquitination proteome data at the network level. This report provides the first integrative description of the protein acetylation and ubiquitination-oriented systematic regulation in human cancer cells.

Chemotherapy in malignant disease

1970 ◽  
Vol 8 (4) ◽  
pp. 13-16
Keyword(s):  
Cancer Cells ◽  
Cancer Chemotherapy ◽  
Anticancer Agents ◽  
Antimicrobial Chemotherapy ◽  
Malignant Disease ◽  
Human Cells ◽  
Normal Cells ◽  
Different Types ◽  
Normal Human ◽  
Normal Human Cells

Cancer chemotherapy, unlike antimicrobial chemotherapy, is not based on absolute metabolic differences between cancer cells and normal human cells. Anticancer agents inhibit the growth of cells, whether normal or malignant, though different types of cell vary in their susceptibility to these agents, and in their capacity for recovery. The usefulness of these drugs is thus limited by their effects on normal cells.

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