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Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications.
BMC Immunol. 2012 Feb 08; 13:7.BI

Abstract

BACKGROUND

Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity.

RESULTS

We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells.

CONCLUSIONS

Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.

Authors+Show Affiliations

Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22316211

Citation

Jimenez-Perez, Miriam I., et al. "Cervical Cancer Cell Lines Expressing NKG2D-ligands Are Able to Down-modulate the NKG2D Receptor On NKL Cells With Functional Implications." BMC Immunology, vol. 13, 2012, p. 7.
Jimenez-Perez MI, Jave-Suarez LF, Ortiz-Lazareno PC, et al. Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications. BMC Immunol. 2012;13:7.
Jimenez-Perez, M. I., Jave-Suarez, L. F., Ortiz-Lazareno, P. C., Bravo-Cuellar, A., Gonzalez-Ramella, O., Aguilar-Lemarroy, A., Hernandez-Flores, G., Pereira-Suarez, A. L., Daneri-Navarro, A., & del Toro-Arreola, S. (2012). Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications. BMC Immunology, 13, 7. https://doi.org/10.1186/1471-2172-13-7
Jimenez-Perez MI, et al. Cervical Cancer Cell Lines Expressing NKG2D-ligands Are Able to Down-modulate the NKG2D Receptor On NKL Cells With Functional Implications. BMC Immunol. 2012 Feb 8;13:7. PubMed PMID: 22316211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications. AU - Jimenez-Perez,Miriam I, AU - Jave-Suarez,Luis F, AU - Ortiz-Lazareno,Pablo C, AU - Bravo-Cuellar,Alejandro, AU - Gonzalez-Ramella,Oscar, AU - Aguilar-Lemarroy,Adriana, AU - Hernandez-Flores,Georgina, AU - Pereira-Suarez,Ana L, AU - Daneri-Navarro,Adrian, AU - del Toro-Arreola,Susana, Y1 - 2012/02/08/ PY - 2011/06/30/received PY - 2012/02/08/accepted PY - 2012/2/10/entrez PY - 2012/2/10/pubmed PY - 2012/9/29/medline SP - 7 EP - 7 JF - BMC immunology JO - BMC Immunol. VL - 13 N2 - BACKGROUND: Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. RESULTS: We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. CONCLUSIONS: Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells. SN - 1471-2172 UR - https://www.unboundmedicine.com/medline/citation/22316211/Cervical_cancer_cell_lines_expressing_NKG2D_ligands_are_able_to_down_modulate_the_NKG2D_receptor_on_NKL_cells_with_functional_implications_ L2 - https://bmcimmunol.biomedcentral.com/articles/10.1186/1471-2172-13-7 DB - PRIME DP - Unbound Medicine ER -