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Exogenous growth hormone promotes an epithelial-mesenchymal hybrid phenotype in cancerous HeLa cells but not in non-cancerous HEK293 cells

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Abstract

In cancer, the Epithelial to Mesenchymal Transition (EMT) is the process in which epithelial cells acquire mesenchymal features that allow metastasis, and chemotherapy resistance. Growth hormone (GH) has been associated with melanoma, breast, and endometrial cancer progression through an autocrine regulation of EMT. Since exogenous and autocrine expression of GH is known to have different molecular effects, we investigated whether exogenous GH is capable of regulating the EMT of cancer cells. Furthermore, we investigated whether exogenous GH could promote EMT in non-cancerous cells. To study the effect of GH (100 ng/ml) on cancer and non-cancer cells, we used HeLa and HEK293 cell lines, respectively. We evaluated the loss of cell–cell contacts, by cell scattering assay and migration by wound-healing assay. Additionally, we evaluated the morphological changes by phalloidin-staining. Finally, we evaluated the molecular markers E-cadherin and vimentin by flow cytometry. GH enhances cell scattering and the migratory rate and promotes morphological changes such as cell area increase and actin cytoskeleton filaments formation on HeLa cell line. Moreover, we found that GH favors the expression of the mesenchymal protein vimentin, followed by an increase in E-cadherin's epithelial protein expression, characteristics of an epithelial-mesenchymal hybrid phenotype that is associated with metastasis. On HEK293cells, GH promotes morphological changes, including cell area increment and filopodia formation, but not affects scattering, migration, nor EMT markers expression. Our results suggest that exogenous GH might participate in cervical cancer progression favoring a hybrid EMT phenotype but not on non-cancerous HEK293 cells.

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Acknowledgements

The authors thank Jonathan García Román, PhD., for his kind review of the final version of this manuscript. In addition, Olascoaga-Caso acknowledges the support from Consejo Nacional de Ciencia y Tecnología (CONACyT) for the doctoral scholarship assigned with the number 297526.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. PhD Health Sciences Program. Universidad Veracruzana, Xalapa, Veracruz, Mexico

    E. M. Olascoaga-Caso

  2. Cell Culture Laboratory, Department of Biomedicine, Instituto de Ciencias de la Salud, Universidad Veracruzana, Av. Luis Castelazo-Ayala S/N, Industrial-Animas, 91190, Xalapa, Veracruz, Mexico

    E. M. Olascoaga-Caso, E. Tamariz-Domínguez & E. Juárez-Aguilar

  3. Flow Cytometry Unity, Department of Biomedicine, Instituto de Ciencias de la Salud, Universidad Veracruzana, Médicos y odontólogos s/n, Unidad del Bosque, 91010, Xalapa, Veracruz, Mexico

    J. C. Rodríguez-Alba

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Contributions

All authors contributed to the study conception and experimental design. Data collection was performed by Olascoaga-Caso. Experimental design and analysis of scattering and migration assays were performed by Juárez-Aguilar and Olascoaga-Caso. Experimental design and analysis of cell morphology were performed by Tamariz-Domínguez and Olascoaga-Caso. Experimental design and analysis of flow cytometry were performed by Rodríguez-Alba and Olascoaga-Caso. The first draft of the manuscript was written by Olascoaga-Caso, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Olascoaga-Caso, E.M., Tamariz-Domínguez, E., Rodríguez-Alba, J.C. et al. Exogenous growth hormone promotes an epithelial-mesenchymal hybrid phenotype in cancerous HeLa cells but not in non-cancerous HEK293 cells. Mol Cell Biochem 478, 1117–1128 (2023). https://doi.org/10.1007/s11010-022-04583-1

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