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Cervical cancer cells induce apoptosis in TCD4+ lymphocytes through the secretion of TGF-β

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Tumor cells are known to secrete cytokines that modify their microenvironment in order to favor their survival and continuous proliferation. In this work, we evaluated if TGF-β secreted in vitro by cervical cancer cells could interfere with the proliferation and survival of lymphocytes.

Methods

Lymphocytes were obtained from peripheral blood of healthy human volunteers, and isolated by density gradient centrifugation and cultured in 96-well plates. Lymphocyte proliferation was induced with phytohemaglutinin and co-cultured with conditioned media (CM) from cervical cancer cell lines, and the inhibition of proliferation was evaluated after 72 h by the incorporated radioactivity and a CFSE-labeling assay. TGF-β quantification on these CM was evaluated by ELISA. Non-apoptotic cellular death was evaluated through disruption of cell membrane integrity by measuring the liberation of lactate dehydrogenase. The apoptosis process was evaluated by annexin-V and active caspase-3. The presence of CD4+ or CD8+ lymphocytes was evaluated by flow cytometry using specific antibodies.

Results

It was found that the conditioned media from these cells significantly inhibited the proliferation of lymphocytes and induced them to go into apoptosis. Antibodies against TGF-β almost completely blocked this activity, suggesting that this cytokine is responsible for the inhibitory activity. When the induced apoptosis on subpopulations of lymphocytes was evaluated, it was detected that the CD4+ cells were specifically targeted.

Conclusions

Cervical cancer cells secrete TGF-β that inhibits lymphocyte proliferation and induces apoptosis in CD4+, but not in CD8+ lymphocytes.

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Acknowledgments

This paper constitutes a partial fulfilment of the Graduate Program in Biological Sciences of the National Autonomous University of México (UNAM, 04510), acknowledges the scholarship and financial support provided by the National Council of Science and Technology (CONACyT), and PAPIME PE206812, UNAM. The authors would like to thank Dr. Dionisio Parra (Gynecoperinatology Department), Dr. Victor García (Teaching Department), Hospital General “Ignacio Zaragoza” ISSSTE, for technical cooperation.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Unidad de Investigación en Diferenciación Celular y Cáncer, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, 09230, Mexico D.F., Mexico

    Hugo López-Muñoz, José M. V. Hernández-Vazquez, Benny Weiss-Steider & Luis Sánchez-Sánchez

  2. Departamento de Biología Celular. Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico D.F., Mexico

    Ma. Luisa Escobar-Sánchez

  3. Departamento de Biología Celular, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico, Mexico

    Rebeca López-Marure

  4. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico D.F., Mexico

    Ricardo Lascurain-Ledesma & Edgar Zenteno

Authors
  1. Hugo López-Muñoz
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  2. Ma. Luisa Escobar-Sánchez
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  3. Rebeca López-Marure
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  4. Ricardo Lascurain-Ledesma
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  5. Edgar Zenteno
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  6. José M. V. Hernández-Vazquez
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  7. Benny Weiss-Steider
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  8. Luis Sánchez-Sánchez
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Corresponding author

Correspondence to Luis Sánchez-Sánchez.

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López-Muñoz, H., Escobar-Sánchez, M.L., López-Marure, R. et al. Cervical cancer cells induce apoptosis in TCD4+ lymphocytes through the secretion of TGF-β. Arch Gynecol Obstet 287, 755–763 (2013). https://doi.org/10.1007/s00404-012-2621-y

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  • DOI: https://doi.org/10.1007/s00404-012-2621-y

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