PhD Health Sciences Program. Universidad Veracruzana, Xalapa, Veracruz, Mexico.
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.
Mol Cell Biochem. 2023 May;478(5):1117-1128. doi: 10.1007/s11010-022-04583-1. Epub 2022 Oct 12.
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.
在癌症中，上皮细胞向间充质转化（EMT）是上皮细胞获得允许转移和化疗耐药的间充质特征的过程。生长激素（GH）已通过 EMT 的自分泌调节与黑色素瘤、乳腺癌和子宫内膜癌的进展相关。由于外源性和内源性 GH 的表达具有不同的分子效应，我们研究了外源性 GH 是否能够调节癌细胞的 EMT。此外，我们还研究了外源性 GH 是否能够促进非癌细胞的 EMT。为了研究 GH（100ng/ml）对癌细胞和非癌细胞的影响，我们分别使用了 HeLa 和 HEK293 细胞系。我们通过细胞散射实验和划痕愈合实验评估了细胞-细胞接触的丧失，通过鬼笔环肽染色评估了形态变化。最后，我们通过流式细胞术评估了 E-钙粘蛋白和波形蛋白等分子标志物的表达。GH 增强了 HeLa 细胞系的细胞散射和迁移率，并促进了形态变化，如细胞面积增加和肌动蛋白细胞骨架丝的形成。此外，我们发现 GH 有利于间充质蛋白波形蛋白的表达，随后上皮蛋白 E-钙粘蛋白的表达增加，这是一种与转移相关的上皮-间充质混合表型的特征。在 HEK293 细胞中，GH 促进形态变化，包括细胞面积增加和丝状伪足形成，但不影响散射、迁移或 EMT 标志物的表达。我们的结果表明，外源性 GH 可能参与宫颈癌的进展，有利于混合 EMT 表型，但对非癌细胞 HEK293 细胞没有影响。
