scholarly journals The Role of Acrolein and NADPH Oxidase in the Granulocyte-Mediated Growth-Inhibition of Tumor Cells

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 292 ◽  
Author(s):  
Morana Jaganjac ◽  
Tanja Matijevic Glavan ◽  
Neven Zarkovic
Keyword(s):  
Nadph Oxidase ◽  
Tumor Cell ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Redox Homeostasis ◽  
Peroxidation Of Lipids ◽  
Tlr4 Expression ◽  
Antitumor Effects ◽  
Reactive Aldehydes

: Although granulocytes are the most abundant leukocytes in human blood, their involvement in the immune response against cancer is not well understood. While granulocytes are known for their “oxidative burst” when challenged with tumor cells, it is less known that oxygen-dependent killing of tumor cells by granulocytes includes peroxidation of lipids in tumor cell membranes, yielding formation of reactive aldehydes like 4-hydroxynonenal (4-HNE) and acrolein. In the present work, we investigate the role of reactive aldehydes on cellular redox homeostasis and surface toll-like receptor 4 (TLR4) expression. We have further study the granulocyte-tumor cell intercellular redox signaling pathways. The data obtained show that granulocytes in the presence of 4-HNE and acrolein induce excessive ROS formation in tumor cells. Acrolein was also shown to induce granulocyte TLR4 expression. Furthermore, granulocyte-mediated antitumor effects were shown to be mediated via HOCl intracellular pathway by the action of NADPH oxidase. However, further studies are needed to understand interaction between TLR4 and granulocyte-tumor cell intercellular signaling pathways.

Current Study of RhoA and Associated Signaling Pathways in Gastric Cancer

2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Actin Polymerization ◽  
Cell Transformation ◽  
Cell Movement ◽  
Invasion And Metastasis ◽  
Common Cancer

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.

scholarly journals RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen-Chen Huang ◽  
Fang-Rui Liu ◽  
Qiang Feng ◽  
Xin-Yan Pan ◽  
Shu-Ling Song ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Membrane ◽  
Fusion Protein ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fusion Proteins ◽  
Inhibitory Effect ◽  
Endosomal Escape ◽  
Antitumor Effects ◽  
Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

scholarly journals Inhibition Effect of Chloroquine and Integrin-Linked Kinase Knockdown on Translation in Melanoma Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3682
Author(s):  
Dorota Gil ◽  
Piotr Laidler ◽  
Marta Zarzycka ◽  
Joanna Dulińska-Litewka
Keyword(s):  
Signaling Pathways ◽  
Melanoma Cell ◽  
Melanoma Cells ◽  
Antitumor Effects ◽  
Regulatory Pathways ◽  
Scratch Wound ◽  
Integrin Linked Kinase ◽  
And Migration ◽  
Cell Signaling Pathways

The twofold role of autophagy in cancer is often the therapeutic target. Numerous regulatory pathways are shared between autophagy and other molecular processes needed in tumorigenesis, such as translation or survival signaling. Thus, we have assumed that ILK knockdown should promote autophagy, and used together with chloroquine, an autophagy inhibitor, it could generate a better anticancer effect by dysregulation of common signaling pathways. Expression at the protein level was analyzed using Western Blot; siRNA transfection was done for ILK. Analysis of cell signaling pathways was monitored with phospho-specific antibodies. Melanoma cell proliferation was assessed with the crystal violet test, and migration was evaluated by scratch wound healing assays. Autophagy was monitored by the accumulation of its marker, LC3-II. Our data show that ILK knockdown by siRNA suppresses melanoma cell growth by inducing autophagy through AMPK activation, and simultaneously initiates apoptosis. We demonstrated that combinatorial treatment of melanoma cells with CQ and siILK has a stronger antitumor effect than monotherapy with either of these. It generates the synergistic antitumor effects by the decrease of translation of both global and oncogenic proteins synthesis. In our work, we point to the crosstalk between translation and autophagy regulation.

scholarly journals Hepatocyte-tumor cell interaction in vitro. I. Conditions for rosette formation and inhibition by anti-H-2 antibody.

1980 ◽  
Vol 151 (4) ◽  
pp. 984-989 ◽  
Author(s):  
V Schirrmacher ◽  
R Cheingsong-Popov ◽  
H Arnheiter
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Metastatic Tumor ◽  
Cell Interaction ◽  
Rosette Formation ◽  
Normal Cells ◽  
Neuraminidase Treatment

Murine hepatocytes, isolated by an in situ collagenase-perfusion technique and cultured in Petri dishes, were shown to form rosettes with liver-metastasizing syngeneic tumor cells. Pretreatment of the tumor cells with neuraminidase generally increased the binding, whereas pretreatment of the liver cells with neuraminidase abolished the binding completely. The tumor-cell binding may be mediated by the previously described lectin-like receptor of hepatocytes that also was sensitive to neuraminidase treatment and that bound desialylated cells better than normal cells. Anti-H-2 sera could efficiently inhibit the rosette formation of metastatic tumor cells with the hepatocytes, which points to a possible role of H-2 molecules in this interaction of neoplastic and normal cells.

Unique Pattern of Raf-1 Kinase Inhibitory Protein (RKIP) Expression in Multiple Myeloma (MM) Compared to Other Tumor Types: Overexpression of RKIP and a Phosphorylated RKIP Is Common in MM Tumor Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4852-4852
Author(s):  
Stavroula Baritaki ◽  
Sara Huerta-Yepez ◽  
Kam Yeung ◽  
Manuel Penichet ◽  
Haiming Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cell ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Cell Lines ◽  
Immune Surveillance ◽  
Myeloma Cell ◽  
Inhibitory Protein ◽  
Multiple Myeloma Cell ◽  
Survival Signaling

Abstract Objective and Rationale Raf-1 kinase inhibitory protein (RKIP) is a modulator of cell signaling and survival that functions as an endogenous inhibitor of multiple kinases, including kinases involved in the Raf/MEK/ERK and NF-κB pathways. RKIP has been identified as a metastasis suppressor gene and an immune surveillance cancer gene, since loss of RKIP protein expression has been associated with tumor progression, metastasis and escape from immune surveillance. Further, RKIP expression has been associated with prognostic significance in many cancers. Recently, we have demonstrated that induction of RKIP expression in tumors with low RKIP levels results in increased tumor cell sensitivity to immuno- or chemo-therapy via inhibition of the above pathways. However, multiple myeloma (MM) cells have been shown to express high RKIP levels compared to other tumors and still remain highly resistant to conventional cytotoxic therapies. These findings were unexpected and thus, it was plausible that the high level of RKIP expression was not functionally active. It has been reported that phosphorylation of RKIP at Ser-153 renders the cells inactive (Rosner et al., 2003, J Biol Chem 278:13061–8). Thus, we examined the expression and the phosphorylation status of the RKIP protein in several multiple myeloma cell lines and tissues and compared them with other cell lines with low RKIP expression. Hypothesis We hypothesized that MM tumor cells express high levels of the inactive phoshorylated RKIP protein which antagonizes the active non-phoshorylated RKIP form in the inhibition of the survival signaling pathways. Experimental Designs and Methods Multiple myeloma (IM-9, RPMI 8226, MM1S, U266 cell lines and fresh bone marrow samples from MM patients), PC-3 prostatic carcinoma and Ramos B-NHL cell lines were examined for total and phosphorylated RKIP expression by IHC and Western Blot analyses. The total RKIP protein was significantly elevated in multiple myeloma cell lines compared to the prostate and B-NHL lines. The predominant RKIP form in multiple myeloma tumors was the phosphorylated RKIP protein with high nuclear localization, as assessed by IHC, while the phosphorylated RKIP levels in the non-myeloma tumors were relatively low. It has been reported that the phosphorylation of RKIP is mediated by protein kinase C (Rosner et al., 2003, J Biol Chem 278:13061–8). Additional studies in multiple myeloma cell lines also revealed high expression of the zeta isoform of PKC (PKCζ), known to phosphorylate and inactivate RKIP. Conclusions and Implications The present findings demonstrate that the aberrant RKIP phosphorylation in multiple myeloma tumors may result in the inhibition of the suppressive effect of RKIP on tumor survival signaling pathways. We postulate that the high expression of RKIP may be due to inhibition of proteasome degradation. The present findings also suggest that screening of RKIP levels and RKIP phosphorylation status in MM may be useful as prognostic factors of tumor cell response to anti-tumor therapies.

scholarly journals Role of 99mTc-(V)DMSA in Detecting Tumor Cell Proliferation

2007 ◽  
Vol 2 ◽  
pp. 117739010700200 ◽  
Author(s):  
Fatma Al-Saeedi
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Dimercaptosuccinic Acid ◽  
Cell Detection ◽  
Tumor Cell Proliferation ◽  
Technetium 99M ◽  
Tumor Cell Detection ◽  
Technetium 99M Dimercaptosuccinic Acid

Pentavalent technetium-99m dimercaptosuccinic acid (99mTc-(V)DMSA) is a tumor-seeking agent which was introduced to evaluate, image, and manage many types of cancers. In this review, the beginning of, and the most recent applications of using this agent was appraised. The relation with tumor cell detection and proliferation was reported and several mechanisms of uptake of 99mTc-(V)DMSA in tumor cells are described.

scholarly journals Breast tumor cell-specific knockout of Twist1 inhibits cancer cell plasticity, dissemination, and lung metastasis in mice

2017 ◽  
Vol 114 (43) ◽  
pp. 11494-11499 ◽  
Author(s):  
Yixiang Xu ◽  
Dong-Kee Lee ◽  
Zhen Feng ◽  
Yan Xu ◽  
Wen Bu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Lung Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Early Stage ◽  
Migration And Invasion ◽  
Small Subset ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Twist1 is an epithelial–mesenchymal transition (EMT)-inducing transcription factor (TF) that promotes cell migration and invasion. To determine the intrinsic role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we developed mouse models with an oncogene-induced mammary tumor containing wild-type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1TKO). Twist1 knockout showed no effects on tumor initiation and growth. In both models with early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and lung metastasis was absent. Twist1 expression was detected in ∼6% of the advanced WT tumor cells. Most of these Twist1+ cells coexpressed several other EMT-inducing TFs (Snail, Slug, Zeb2), lost ERα and luminal marker K8, acquired basal cell markers (K5, p63), and exhibited a partial EMT plasticity (E-cadherin+/vimentin+). In advanced Twist1TKO tumor cells, Twist1 knockout largely diminished the expression of the aforementioned EMT-inducing TFs and basal and mesenchymal markers, but maintained the expression of the luminal markers. Circulating tumor cells (CTCs) were commonly detected in mice with advanced WT tumors, but not in mice with advanced Twist1TKO tumors. Nearly all WT CTCs coexpressed Twist1 with other EMT-inducing TFs and both epithelial and mesenchymal markers. Mice with advanced WT tumors developed extensive lung metastasis consisting of luminal tumor cells with silenced Twist1 and mesenchymal marker expression. Mice with advanced Twist1TKO tumors developed very little lung metastasis. Therefore, Twist1 is required for the expression of other EMT-inducing TFs in a small subset of tumor cells. Together, they induce partial EMT, basal-like tumor progression, intravasation, and metastasis.

scholarly journals Activation of the NF-κB Signaling Pathway Promotes Malignancy in Bladder Cancer Cells in a Positive Feedback Manner

2020 ◽  
Author(s):  
Zhenfeng guan ◽  
Yi Sun ◽  
YaZhuo Jiang ◽  
Xinyang Wang ◽  
Jinhai Fan
Keyword(s):  
Bladder Cancer ◽  
Endothelial Cells ◽  
Tumor Cell ◽  
Tumor Progression ◽  
Signaling Pathway ◽  
Tumor Cells ◽  
Positive Feedback ◽  
Umbilical Vein

Abstract Background: The main issue arising from bladder cancer (BCa) is the high relapse ratio and tumor progression, the mechanism of which remains to be elucidated. Interaction of tumor cells with the stroma of microenvironment promoting tumor progression warrants much attention from researchers. Among all stromal cells, endothelial cells (ECs) are exceptional. Numerous studies have investigated its role of angiogenesis, but have not studied immunocyte recruitment and chemokine secretion, the important significance of which in tumor progression has been proven. Meanwhile, to the best of our knowledge, few studies have focused on the direct interaction between tumor cells and ECs in BCa tissue, which was the aim of the present study. Methods: In the present study, immunohistochemical staining is used for detecting the distribution of ECs in BCa tissue, and we use SPSS 19 to analysis the relationship between ECs distribution and tumor grade/stage; inadition, co-curlturing of tumor cell with ECs is usd to mimicking the interaction of tumor cell with ECs, followed by Chamber Assay, BrdU incorporoartion, WB, Qt-PCR, ect, to investiatin the mechanism. Results: The distribution of ECs in BCa tissue is significantly increased according to BCa grade and negatively associated to the time from BCa diagnosis to progression, manifesting as an independent risk factor for BCa prognosis. The following in vitro experiment indicates that the conditional medium from co-culture of tumor cells (T24/J82) with ECs (human umbilical vein endothelial cells, which were used as ECs in the in vitro experiment) contributes to the activation of the NF-ĸB signaling pathway in tumor cells, leading to the upregulation of CXCL1/8. This further results in enhanced tumor cell malignancy and EC recruitment, manifested as a positive feedback loop. Conclusions: The present study provided a further understanding on the role of ECs in BCa progression—not only by angiogenesis but also by interacting with tumor cell dirctly.

PTEN and Autism With Macrocepaly

2013 ◽  
Author(s):  
Craig M. Powell
Keyword(s):  
Tumor Cell ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Clinical Phenotype ◽  
Model Systems ◽  
Tumor Cell Lines ◽  
Gene Encoding ◽  
Increased Risk ◽  
The Brain

Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN) is a gene encoding an intracellular signaling molecule. PTEN was originally discovered as the gene responsible for a subset of familial hamartoma (tumor) syndromes associated with increased risk for certain cancers (Nelen et al., 1997) and as a gene often mutated in human cancers and tumor cell lines (Li et al., 1997; Steck et al., 1997). More recently, mutations in PTEN have been linked genetically to the clinical phenotype of autism or developmental delay with macrocephaly (Boccone et al., 2006; Butler et al., 2005; Buxbaum et al., 2007; Goffin, Hoefsloot, Bosgoed, Swillen, & Fryns, 2001; Herman, Butter, et al., 2007; McBride et al., 2010; Orrico et al., 2009; Stein, Elias, Saenz, Pickler, & Reynolds, 2010; Varga, Pastore, Prior, Herman, & McBride, 2009; Zori, Marsh, Graham, Marliss, & Eng, 1998). This chapter examines the role of PTEN in intracellular signaling, the link between PTEN signaling pathways and other autism-related genes and signaling pathways, the genetic relationship between PTEN and autism, model systems in which effects of Pten deletion on the brain have been studied, and promising preclinical data identifying therapeutic targets for patients with autism/macrocephaly associated with PTEN mutations.

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