scholarly journals Release of cell surface proteoglycans from differentiating colon cells proceeds by cleavage of lipophilic anchor peptides

1992 ◽  
Vol 287 (1) ◽  
pp. 131-140 ◽  
Author(s):  
J A McBain ◽  
G C Mueller
Keyword(s):  
Colon Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Heparan Sulphate ◽  
Buoyant Density ◽  
Terminal Differentiation ◽  
Proteinase K ◽  
Colon Cancer Cells ◽  
Colon Cells ◽  
Core Proteins

Heparan sulphate proteoglycans are rapidly released from VACO 10MS colon cancer cells that are triggered with phorbol esters to undergo terminal differentiation. This lag-free temperature-sensitive process is correlated with a conversion of the lipophilic proteoglycans of the cell surface into non-lipophilic proteoglycans that accumulate in the culture medium. The released proteoglycans are very similar to their lipophilic precursors in size, buoyant density and glycosaminoglycan characteristics; however, they exhibit slightly smaller core proteins after chemical and enzymic deglycosylation. The lipophilicity of the larger-sized core proteins of the cell-associated proteoglycans is also correlated with the presence of an easily iodinatable domain; this domain is missing in the released proteoglycans. Exogenous proteases (i.e. chymotrypsin, V8, trypsin and proteinase K) readily cleave this segment from the larger protease-resistant region of the proteoglycan structure. It is also released intact by treatment of the isolated proteoglycans with methanolic HCl. This component appears to be peptide in character, in that proteases readily degrade it and release iodotyrosines when the precursor has been iodinated. No evidence for the presence of covalently attached fatty acids in the cell-associated proteoglycans was found. These results are consistent with the hypothesis that the altered proteoglycan metabolism that is associated with the phorbol-ester-induced terminal differentiation of certain human colon cancer cells ensues upon the activation of a membrane-localized protease that cleaves a lipophilic anchor segment from the cell surface proteoglycans.

scholarly journals Destruxin B Suppresses Drug-Resistant Colon Tumorigenesis and Stemness Is Associated with the Upregulation of miR-214 and Downregulation of mTOR/β-Catenin Pathway

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 353 ◽  
Author(s):  
Szu-Yuan Wu ◽  
Yan-Jiun Huang ◽  
Yew-Min Tzeng ◽  
Chi-Ying Huang ◽  
Michael Hsiao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Side Population ◽  
Colon Cancer Cells ◽  
Cancer Stemness ◽  
Colon Cells ◽  
Colon Tumorigenesis ◽  
Tumor Sphere ◽  
Sphere Formation

Background: Drug resistance represents a major challenge for treating patients with colon cancer. Accumulating evidence suggests that Insulin-like growth factor (IGF)-associated signaling promotes colon tumorigenesis and cancer stemness. Therefore, the identification of agents, which can disrupt cancer stemness signaling, may provide improved therapeutic efficacy. Methods: Mimicking the tumor microenvironment, we treated colon cancer cells with exogenous IGF1. The increased stemness of IGF1-cultured cells was determined by ALDH1 activity, side-population, tumor sphere formation assays. Destruxin B (DB) was evaluated for its anti-tumorigenic and stemness properties using cellular viability, colony-formation tests. The mimic and inhibitor of miR-214 were used to treat colon cancer cells to show its functional association to DB treatment. In vivo mouse models were used to evaluate DB’s ability to suppress colon tumor-initiating ability and growth inhibitory function. Results: IGF1-cultured colon cancer cells showed a significant increase in 5-FU resistance and enhanced stemness properties, including an increased percentage of ALDH1+, side-population cells, tumor sphere generation in vitro, and increased tumor initiation in vivo. In support, using public databases showed that increased IGF1 expression was significantly associated with a poorer prognosis in patients with colon cancer. DB, a hexadepsipeptide mycotoxin, was able to suppress colon tumorigenic phenotypes, including colony and sphere formation. The sequential treatment of DB, followed by 5-FU, synergistically inhibited the viability of colon cancer cells. In vivo studies showed that DB suppressed the tumorigenesis by 5-FU resistant colon cells, and in a greater degree when combined with 5-FU. Mechanistically, DB treatment was associated with decreased the mammalian target of rapamycin (mTOR) and β-catenin expression and an increased miR-214 level. Conclusion: We provided evidence of DB as a potential therapeutic agent for overcoming 5-FU resistance induced by IGF1, and suppressing cancer stem-like properties in association with miR-214 regulation. Further investigation is warranted for its translation to clinical application.

scholarly journals The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand.

1996 ◽  
Vol 184 (3) ◽  
pp. 1075-1082 ◽  
Author(s):  
J O'Connell ◽  
G C O'Sullivan ◽  
J K Collins ◽  
F Shanahan
Keyword(s):  
Colon Cancer ◽  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Cancer Cells ◽  
Antisense Oligonucleotide ◽  
Fas Ligand ◽  
Immune Privilege ◽  
Colon Cancer Cells ◽  
Rt Pcr

Tumors escape immunological rejection by a diversity of mechanisms. In this report, we demonstrate that the colon cancer cell SW620 expresses functional Fas ligand (FasL), the triggering agent of Fas receptor (FasR)-mediated apoptosis within the immune system. FasL mRNA and cell surface FasL were detected in SW620 cells using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. We show that SW620 kills Jurkat T cells in a Fas-mediated manner. FasR-specific antisense oligonucleotide treatment, which transiently inhibited FasR expression, completely protected Jurkat cells from killing by SW620. FasL-specific antisense oligonucleotide treatment of SW620 inhibited its Jurkat-killing activity. FasL has recently been established as a mediator of immune privilege in mouse retina and testis. Our finding that colon cancer cells express functional FasL suggests it may play an analogous role in bestowing immune privilege on human tumors. HT29 and SW620 colon cancer cells were found to express FasR mRNA and cell surface FasR using RT-PCR and immunofluorescence flow cytometry, respectively. However, neither of these cells underwent apoptosis after treatment by the anti-FasR agonistic monoclonal antibody CH11. Our results therefore suggest a Fas counterattack model for immune escape in colon cancer, whereby the cancer cells resist Fas-mediated T cell cytotoxicity but express functional FasL, an apoptotic death signal to which activated T cells are inherently sensitive.

scholarly journals CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties

2021 ◽  
Vol 9 ◽  
Author(s):  
Shudong Zhu ◽  
Yan Zhu ◽  
Qiuwen Wang ◽  
Yi Zhang ◽  
Xialing Guo
Keyword(s):  
Dna Methylation ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Human Colon ◽  
Dna Methyltransferases ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Colon Cells ◽  
Matrigel Invasion

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.

A novel apoptosis-inducing monoclonal antibody (anti-LHK) against a cell surface antigen on colon cancer cells

2005 ◽  
Vol 40 (10) ◽  
pp. 945-955 ◽  
Author(s):  
Hidehiko Matsukawa ◽  
Takanori Kanai ◽  
Makoto Naganuma ◽  
Nobuhiko Kamada ◽  
Tadakazu Hisamatsu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Colon Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Surface Antigen ◽  
Cell Surface Antigen ◽  
Colon Cancer Cells ◽  
A Cell

scholarly journals A Nudibranch Marine Extract Selectively Chemosensitizes Colorectal Cancer Cells by Inducing ROS-Mediated Endoplasmic Reticulum Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Verónica Ruiz-Torres ◽  
Nicholas Forsythe ◽  
Almudena Pérez-Sánchez ◽  
Sandra Van Schaeybroeck ◽  
Enrique Barrajón-Catalán ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Human Colon ◽  
Resistance Mechanisms ◽  
Colon Cancer Cells ◽  
Colon Cells ◽  
Lower Effect ◽  
The Unfolded Protein Response

The present study shows the putative antiproliferative mechanism of action of the previously analytically characterized nudibranch extract ( Dolabella auricularia, NB) and its different effects in colon cancer cells vs. nontumor colon cells. NB extract increased the accumulation of reactive oxygen species (ROS) and increased endoplasmic reticulum (ER) stress via stimulation of the unfolded protein response. Stress scavengers, N-acetylcysteine (NAC) and 4-phenylbutyric acid (4-PBA), decreased the stress induced by NB. The results showed that NB extract increased ER stress through overproduction of ROS in superinvasive colon cancer cells, decreased their resistance threshold, and produced a nonreturn level of ER stress, causing DNA damage and cell cycle arrest, which prevented them from achieving hyperproliferative capacity and migrating to and invading other tissues. On the contrary, NB extract had a considerably lower effect on nontumor human colon cells, suggesting a selective effect related to stress balance homeostasis. In conclusion, our results confirm that the growth and malignancy of colon cancer cells can be decreased by marine compounds through the modification of one of the most potent resistance mechanisms present in tumor cells; this characteristic differentiates cancer cells from nontumor cells in terms of stress balance.

Human fetal colon cells and colon cancer cells respond differently to butyrate and PUFAs

2009 ◽  
Vol 53 (S1) ◽  
pp. S102-S113 ◽  
Author(s):  
Jiřina Hofmanová ◽  
Alena Vaculová ◽  
Zuzana Koubková ◽  
Martina Hýžd'alová ◽  
Alois Kozubík
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Colon Cells

scholarly journals Expression of circular RNA CDR1‑AS in colon cancer cells increases cell surface PD‑L1 protein levels

2019 ◽  
Author(s):  
Eri Tanaka ◽  
Yu Miyakawa ◽  
Takahiro Kishikawa ◽  
Takahiro Seimiya ◽  
Takuma Iwata ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Surface ◽  
Cancer Cells ◽  
Circular Rna ◽  
Colon Cancer Cells ◽  
Protein Levels ◽  
L1 Protein
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