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Article

Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells

  • Authors:
    • Alejandro Godoy-Pacheco
    • Mariel García-Chagollán
    • Adrián Ramírez-De-Arellano
    • Christian David Hernández-Silva
    • Julio César Villegas-Pineda
    • Inocencia Guadalupe Ramírez-López
    • José Sergio Zepeda-Nuño
    • Adriana Aguilar-Lemarroy
    • Ana Laura Pereira-Suárez
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, University Center for Health Sciences, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico, Institute for Research in Biomedical Sciences, University Center for Health Sciences, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico, Center for Research and Diagnosis of Pathology, Department of Microbiology and Pathology, University Center of Health Sciences, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico, Department of Immunology, Western Biomedical Research Center, Guadalajara, Jalisco 44340, Mexico
  • Article Number: 288
    |
    Published online on: June 28, 2022
       https://doi.org/10.3892/ol.2022.13408
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Abstract

Natural killer (NK) cells play a crucial role in cervical cancer (CC). As estrogens and prolactin (PRL) have been reported to be involved in CC, the present study attempted to elucidate the effects of both hormones on NK cells in CC. For this purpose, NKL cells, as well as CC‑derived cell lines (HeLa, SiHa and C33A) and non‑tumorigenic keratinocytes (HaCaT cells) were stimulated with 17β‑estradiol (E2; 10 nM), PRL (200 ng/ml), or both (E2 and PRL) for 48 h. The expression of hormone receptors (estrogen receptor α and β, G protein‑coupled estrogen receptor 1 and PRL receptor) and NK cell activating receptors [natural killer group 2D (NKG2D), natural cytotoxicity triggering receptor 3, natural cytotoxicity triggering receptor 2 and natural cytotoxicity triggering receptor 1] were measured using western blot analysis and flow cytometry, respectively. In the HeLa, SiHa, C33A and HaCaT cells stimulated with the hormones, the expression of NKG2D ligands [MHC class I polypeptide‑related sequence A/B (MICA/B)] on the membrane and the soluble form of MICA was evaluated using flow cytometry and ELISA. Cytotoxicity assay was performed using GFP‑transfected K562 cells as target cells. E2 reduced NKL cell‑mediated cytotoxicity, while PRL exerted the opposite effect. NKL cells expressed different hormone receptor forms, of which PRL only induced a decrease in NKG2D expression compared to the untreated control NKL cells. PRL increased MICA/B expression in HeLa cells and E2 and PRL reversed this effect. However, in SiHa cells, the concurrent incubation with the two hormones decreased MICA/B expression. E2 and PRL, either alone or in combination, decreased soluble MICA secretion in all CC cell lines, while E2 solely increased soluble MICA secretion in SiHa cells. On the whole, the present study provides evidence that E2 and PRL mediate the mechanisms through which NK and CC cells mediate a cytotoxic response and these have an antagonistic effect on NK cell‑mediated cytotoxicity.
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Copy and paste a formatted citation
Spandidos Publications style
Godoy-Pacheco A, García-Chagollán M, Ramírez-De-Arellano A, Hernández-Silva CD, Villegas-Pineda JC, Ramírez-López IG, Zepeda-Nuño JS, Aguilar-Lemarroy A and Pereira-Suárez AL: Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells. Oncol Lett 24: 288, 2022.
APA
Godoy-Pacheco, A., García-Chagollán, M., Ramírez-De-Arellano, A., Hernández-Silva, C.D., Villegas-Pineda, J.C., Ramírez-López, I.G. ... Pereira-Suárez, A.L. (2022). Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells. Oncology Letters, 24, 288. https://doi.org/10.3892/ol.2022.13408
MLA
Godoy-Pacheco, A., García-Chagollán, M., Ramírez-De-Arellano, A., Hernández-Silva, C. D., Villegas-Pineda, J. C., Ramírez-López, I. G., Zepeda-Nuño, J. S., Aguilar-Lemarroy, A., Pereira-Suárez, A. L."Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells". Oncology Letters 24.2 (2022): 288.
Chicago
Godoy-Pacheco, A., García-Chagollán, M., Ramírez-De-Arellano, A., Hernández-Silva, C. D., Villegas-Pineda, J. C., Ramírez-López, I. G., Zepeda-Nuño, J. S., Aguilar-Lemarroy, A., Pereira-Suárez, A. L."Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells". Oncology Letters 24, no. 2 (2022): 288. https://doi.org/10.3892/ol.2022.13408
Copy and paste a formatted citation
x
Spandidos Publications style
Godoy-Pacheco A, García-Chagollán M, Ramírez-De-Arellano A, Hernández-Silva CD, Villegas-Pineda JC, Ramírez-López IG, Zepeda-Nuño JS, Aguilar-Lemarroy A and Pereira-Suárez AL: Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells. Oncol Lett 24: 288, 2022.
APA
Godoy-Pacheco, A., García-Chagollán, M., Ramírez-De-Arellano, A., Hernández-Silva, C.D., Villegas-Pineda, J.C., Ramírez-López, I.G. ... Pereira-Suárez, A.L. (2022). Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells. Oncology Letters, 24, 288. https://doi.org/10.3892/ol.2022.13408
MLA
Godoy-Pacheco, A., García-Chagollán, M., Ramírez-De-Arellano, A., Hernández-Silva, C. D., Villegas-Pineda, J. C., Ramírez-López, I. G., Zepeda-Nuño, J. S., Aguilar-Lemarroy, A., Pereira-Suárez, A. L."Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells". Oncology Letters 24.2 (2022): 288.
Chicago
Godoy-Pacheco, A., García-Chagollán, M., Ramírez-De-Arellano, A., Hernández-Silva, C. D., Villegas-Pineda, J. C., Ramírez-López, I. G., Zepeda-Nuño, J. S., Aguilar-Lemarroy, A., Pereira-Suárez, A. L."Differential modulation of natural killer cell cytotoxicity by 17β‑estradiol and prolactin through the NKG2D/NKG2DL axis in cervical cancer cells". Oncology Letters 24, no. 2 (2022): 288. https://doi.org/10.3892/ol.2022.13408
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