Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

BMC Immunology

Susana del Toro-Arreola³  Adrian Daneri-Navarro³  Ana L Pereira-Suarez³  Georgina Hernandez-Flores²  Adriana Aguilar-Lemarroy²  Oscar Gonzalez-Ramella³  Alejandro Bravo-Cuellar¹  Pablo C Ortiz-Lazareno²  Luis F Jave-Suarez²  Miriam I Jimenez-Perez² 

[1] Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico;División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico;Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico

关键词: Cervical cancer;    ULBP;    MICB;    MICA;    NKG2D;    NK cells;   

Others  :  1077943
DOI  :  10.1186/1471-2172-13-7

 received in 2011-06-30, accepted in 2012-02-08,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Jimenez-Perez et al; licensee BioMed Central Ltd.

【 图 表 】

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