scholarly journals Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 66
Author(s):  
Natasha Ustyanovska Avtenyuk ◽  
Ghizlane Choukrani ◽  
Emanuele Ammatuna ◽  
Toshiro Niki ◽  
Ewa Cendrowicz Król ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Phosphatidyl Serine ◽  
Epithelial Cancer ◽  
Cancer Cell Adhesion ◽  
Specific Granules ◽  
Adaptive And Innate Immunity ◽  
Anticancer Immunity ◽  
Tumor Selective ◽  
Selective Activity

In earlier studies, galectin-9 (Gal-9) was identified as a multifaceted player in both adaptive and innate immunity. Further, Gal-9 had direct cytotoxic and tumor-selective activity towards cancer cell lines of various origins. In the current study, we identified that treatment with Gal-9 triggered pronounced membrane alterations in cancer cells. Specifically, phosphatidyl serine (PS) was rapidly externalized, and the anti-phagocytic regulator, CD47, was downregulated within minutes. In line with this, treatment of mixed neutrophil/tumor cell cultures with Gal-9 triggered trogocytosis and augmented antibody-dependent cellular phagocytosis of cancer cells. Interestingly, this pro-trogocytic effect was also due to the Gal-9-mediated activation of neutrophils with upregulation of adhesion markers and mobilization of gelatinase, secretory, and specific granules. These activation events were accompanied by a decrease in cancer cell adhesion in mixed cultures of leukocytes and cancer cells. Further, prominent cytotoxicity was detected when leukocytes were mixed with pre-adhered cancer cells, which was abrogated when neutrophils were depleted. Taken together, Gal-9 treatment potently activated neutrophil-mediated anticancer immunity, resulting in the elimination of epithelial cancer cells.

scholarly journals CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells

2021 ◽  
Author(s):  
Mattias Lepsenyi ◽  
Nader Algethami ◽  
Amr A. Al-Haidari ◽  
Anwar Algaber ◽  
Ingvar Syk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Cancer Cell Adhesion ◽  
And Migration ◽  
Cxcr2 Antagonist

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.

scholarly journals Integrin Trafficking and Tumor Progression

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sejeong Shin ◽  
Laura Wolgamott ◽  
Sang-Oh Yoon
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Adhesion

Integrins are major mediators of cancer cell adhesion to extracellular matrix. Through this interaction, integrins play critical roles in cell migration, invasion, metastasis, and resistance to apoptosis during tumor progression. Recent studies highlight the importance of integrin trafficking, endocytosis and recycling, for the functions of integrins in cancer cells. Understanding the molecular mechanisms of integrin trafficking is pivotal for understanding tumor progression and for the development of anticancer drugs.

scholarly journals The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium

2021 ◽  
Vol 22 (11) ◽  
pp. 6049
Author(s):  
Thomas Brock ◽  
Elisabeth Boudriot ◽  
Anke Klawitter ◽  
Marianne Großer ◽  
Trang T. P. Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Breast Cancer Cell Lines ◽  
Tumor Cell Adhesion ◽  
Cancer Cell Adhesion

During metastasis, cancer cells that originate from the primary tumor circulate in the bloodstream, extravasate, and form micrometastases at distant locations. Several lines of evidence suggest that specific interactions between cancer cells and endothelial cells, in particular tumor cell adhesion to the endothelium and transendothelial migration, play a crucial role in extravasation. Here we have studied the role of vascular endothelial (VE)-cadherin which is expressed aberrantly by breast cancer cells and might promote such interactions. By comparing different human breast cancer cell lines, we observed that the number of cancer cells that adhered to endothelium correlated with VE-cadherin expression levels. VE-cadherin silencing experiments confirmed that VE-cadherin enhances cancer cell adhesion to endothelial cells. However, in contrast, the number of cancer cells that incorporated into the endothelium was not dependent on VE‑cadherin. Thus, it appears that cancer cell adhesion and incorporation are distinct processes that are governed by different molecular mechanisms. When cancer cells incorporated into the endothelial monolayer, they formed VE-cadherin positive contacts with endothelial cells. On the other hand, we also observed tumor cells that had displaced endothelial cells, reflecting either different modes of incorporation, or a temporal sequence where cancer cells first form contact with endothelial cells and then displace them to facilitate transmigration. Taken together, these results show that VE-cadherin promotes the adhesion of breast cancer cells to the endothelium and is involved in the initial phase of incorporation, but not their transmigration. Thus, VE-cadherin might be of relevance for therapeutic strategies aiming at preventing the metastatic spread of breast cancer cells.

Induction of tenascin in cancer cells by interactions with embryonic mesenchyme mediated by a diffusible factor

1993 ◽  
Vol 104 (2) ◽  
pp. 289-296 ◽  
Author(s):  
N. Hiraiwa ◽  
H. Kida ◽  
T. Sakakura ◽  
M. Kusakabe
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Culture Media ◽  
Human Cancer ◽  
Early Stage ◽  
Cancer Cell Lines ◽  
Epithelial Cancer ◽  
Human Cancer Cell Lines

Human cancer cell lines A431 and MCF7, which do not produce tenascin (TN) in vitro, were found to produce TN when injected into nude mice or co-cultured with the embryonic mesenchyme. The TN expression in the developing A431 solid tumor was demonstrated by immunohistochemistry and by in situ hybridization. Human TN was detected in culture media by western blot analysis using human specific monoclonal antibody (RCB-1). During tumorigenesis, in the early stage, mouse TN was actively induced and deposited in the peri- and intertumor spaces surrounding the developing tumor. Two days later, TN derived from human epithelial cancer cells was induced and mainly deposited in the intertumor basement membrane. After this stage, tumor cells were actively producing TN. On the other hand, TN induction in non TN-producing cells, such as A431 and MCF7 cell lines, was also observed in vitro. Although cell lines such as NIH-3T3, phi 2, STO, 2H6, 3E5 and CMT315, had no effect on the TN induction, primary cultured embryonic mesenchyme effectively stimulated the TN expression in the cancer cell lines. This mesenchymal effect decreased with age and was entirely lost postnatally. Furthermore, conditioned media from these embryonic mesenchymes could reproduce the same effects on TN induction as observed in the co-culture study. In conclusion, these findings suggest that TN induction in epithelial cancer cells may depend on interactions with the surrounding environment, that these interactions may be mediated by a soluble factor(s) derived from the surrounding mesenchyme and that the TN induction observed in the tumorigenesis may reflect histogenesis during the embryonic period.

scholarly journals Akt directly regulates focal adhesion kinase through association and serine phosphorylation: implication for pressure-induced colon cancer metastasis

2011 ◽  
Vol 300 (3) ◽  
pp. C657-C670 ◽  
Author(s):  
Shouye Wang ◽  
Marc D. Basson
Keyword(s):  
Colon Cancer ◽  
Cell Adhesion ◽  
Focal Adhesion Kinase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Focal Adhesion ◽  
Cancer Metastasis ◽  
Serine Phosphorylation ◽  
Colon Cancer Cells ◽  
Cancer Cell Adhesion

Although focal adhesion kinase (FAK) is typically considered upstream of Akt, extracellular pressure stimulates cancer cell adhesion via Akt-dependent FAK activation. How Akt regulates FAK is unknown. We studied Akt-FAK interaction in colon cancer cells under 15 mmHg increased extracellular pressure. Pressure enhanced Akt-FAK association, blocked by inhibiting FAK or silencing Akt1 but not Akt2, and stimulated FAK serine phosphorylation in Caco-2 and human colon cancer cells from surgical specimens Akt1-dependently. FAK includes three serine (S517/601/695) and one threonine (T600)-containing consensus sequences for Akt phosphorylation. Studying S–>A nonphosphorylatable point mutants suggests that these sites coordinately upregulate FAK Y397 tyrosine phosphorylation, which conventionally initiates FAK activation, and mediate pressure-induced cancer cell adhesion. FAK(T600A) mutation did not prevent pressure-induced FAK(Y397) phosphorylation or adhesion. Akt1 appeared to directly bind FAK, and this binding did not depend on the FAK autophosphorylation site (Y397). In addition, our results demonstrated that Akt phosphorylated FAK at three novel serine phosphorylation sites, which were also not required for FAK-Akt binding. This novel interaction suggests that FAK and Akt may be dual kinase targets to prevent cancer cell adhesion and metastasis.

N-hexane Extract and Fraction of Green Tea as Antiproliferation of MCM-B2 Breast Cancer Cells In Vitro

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Lisni Noraida Waruwu ◽  
Maria Bintang ◽  
Bambang Pontjo Priosoeryanto
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Green Tea ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Green Tea Extract ◽  
Hexane Fraction ◽  
Phytochemical Screening ◽  
Tea Extract

Green tea (Camellia sinensis) is one of traditional plants that have the potential as an anticancer. The sample used in this research commercial green tea extract. The purpose of this study was to test the antiproliferation activity of green tea extract on breast cancer cell MCM-B2 in vitro. Green tea extract fractionated using three solvents, ie water, ethanol 70%, and n-hexane. Extract and fraction of green tea water have value Lethality Concentration 50 (LC50) more than 1000 ppm. The fraction of ethanol 70% and n-hexane had an LC50 value of 883.48 ppm and 600.56 ppm, respectively. The results of the phytochemical screening of green tea extract are flavonoids, tannins, and saponins, while the phytochemical screening results of n-hexane fraction are flavonoids and tannins. Antiproliferation activity was tested on breast cancer cells MCM-B2 and normal cells Vero by trypan blue staining method. The highest MCM-B2 cell inhibitory activity was achieved at a concentration of 13000 ppm green tea extract and 1000 ppm of n-hexane fraction, 59% and 59%, respectively. The extract and n-hexane fraction of green tea are not toxic to normal Vero cells characterized by not inhibiting normal cell proliferation. Keywords: antiproliferative, cancer cell MCM-B2, commercial green tea, cytotoxicity

Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

2020 ◽  
Vol 20 (23) ◽  
pp. 2070-2079
Author(s):  
Srimadhavi Ravi ◽  
Sugata Barui ◽  
Sivapriya Kirubakaran ◽  
Parul Duhan ◽  
Kaushik Bhowmik
Keyword(s):  
Western Blot ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cancer Cell Lines ◽  
Atm Kinase ◽  
Cytotoxicity Studies

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

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