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01-06-2019 | Dimethyl Fumarate | Original Article

HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells

Authors: Noha Mousaad Elemam, Zaidoon Al-Jaderi, Mahmood Yaseen Hachim, Azzam A. Maghazachi

Published in: Cancer Immunology, Immunotherapy | Issue 6/2019

Abstract

We recently reported that pretreatment of IL-2 activated human natural killer (NK) cells with the drugs dimethyl fumarate (DMF) and monomethyl fumarate (MMF) upregulated the expression of surface chemokine receptor CCR10. Ligands for CCR10, namely CCL27 and CCL28, induced the chemotaxis of these cells. Here, we performed a bioinformatics analysis to see which chemokines might be expressed by the human HCT-116 colorectal cancer cells. We observed that, in addition to CCL27 and CCL28, HCT-116 colorectal cancer cells profoundly express CXCL16 which binds CXCR6. Consequently, NK92 cells were treated with DMF and MMF for 24 h to investigate in vitro chemotaxis towards CXCL16, CCL27, and CCL28. Furthermore, supernatants collected from HCT-116 cells after 24 or 48 h incubation induced the chemotaxis of NK92 cells. Similar to their effects on human IL-2-activated NK cells, MMF and DMF enhanced the expression of CCR10 and CXCR6 in NK92 cells. Neutralizing anti-CXCL16 or anti-CCL28 inhibited the chemotactic effects of 24 and 48 supernatants, whereas anti-CCL27 only inhibited the 48 h supernatant activity, suggesting that 24 h supernatant contains CXCL16 and CCL28, whereas HCT-116 secretes all three chemokines after 48 h in vitro cultures. CXCL16, CCL27, and CCL28, as well as the supernatants collected from HCT-116, induced the mobilization of (Ca)²⁺ in NK92 cells. Cross-desensitization experiments confirmed the results of the chemotaxis experiments. Finally, incubation of NK92 cells with HCT-116 induced the lysis of the tumor cells. In summary, these results might have important implications in directing the anti-tumor effectors NK cells towards tumor growth sites.

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Title: HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells
Authors: Noha Mousaad Elemam
Zaidoon Al-Jaderi
Mahmood Yaseen Hachim
Azzam A. Maghazachi
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Keywords: Dimethyl Fumarate
Colorectal Cancer
Colorectal Cancer
Published in: Cancer Immunology, Immunotherapy / Issue 6/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02319-7

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