Open Access

Differential and divergent activity of insulin‑like growth factor binding protein 6 in platinum‑sensitive versus platinum‑resistant high‑grade serous ovarian carcinoma cell lines

  • Authors:
    • Annamaria Piscazzi
    • Valentina Condelli
    • Fabiana Crispo
    • Anna Rita Daniela Coda
    • Giovanni Calice
    • Giuseppina Bruno
    • Santina Venuto
    • Daniele Tibullo
    • Guido Giordano
    • Michele Pietrafesa
    • Arcangelo Liso
    • Matteo Landriscina
  • View Affiliations

  • Published online on: April 21, 2022     https://doi.org/10.3892/ol.2022.13305
  • Article Number: 185
  • Copyright: © Piscazzi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Insulin‑like growth factor binding protein 6 (IGFBP6) is a secreted protein with a controversial role in human malignancies, being downregulated in most types of human cancer, but upregulated in selected tumors. Ovarian cancer (OC) is a human malignancy characterized by IGFBP6 downregulation; however, the significance of its low expression during ovarian carcinogenesis is still poorly understood. In the present study, IGFBP6 expression and activation of its associated signaling pathway were evaluated in two matched OC cell lines derived from a high‑grade serous OC before and after platinum resistance (PEA1 and PEA2 cells, respectively). A whole genome gene expression analysis was comparatively performed in both cell lines upon IGFBP6 stimulation using Illumina technology. IGFBP6 gene expression data from human OC cases were obtained from public datasets. Gene expression data from public datasets confirmed the downregulation of IGFBP6 in primary and metastatic OC tissues compared with in normal ovarian tissues. The comparative analysis of platinum‑sensitive (PEA1) and platinum‑resistant (PEA2) cell lines showed quantitative and qualitative differences in the activation of IGFBP6 signaling. Notably, IGFBP6 enhanced ERK1/2 phosphorylation only in PEA1 cells, and induced more evident and significant gene expression reprogramming in PEA1 cells compared with in PEA2 cells. Furthermore, the analysis of selected genes modulated by IGFBP6 (i.e., FOS, JUN, TNF, IL6, IL8 and EGR1) exhibited an inverse regulation in PEA1 versus PEA2 cells. In addition, selected hallmarks (TNFA_signaling_via_NFKB, TGF_beta_signaling, P53_pathway) and IL‑6 signaling were positively regulated in PEA1 cells, whereas they were inhibited in PEA2 cells in response to IGFBP6. These data suggested that dysregulation of IGFBP6 signaling may serve a role in the progression of OC, and is likely associated with the development of platinum resistance.
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June-2022
Volume 23 Issue 6

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Spandidos Publications style
Piscazzi A, Condelli V, Crispo F, Coda AR, Calice G, Bruno G, Venuto S, Tibullo D, Giordano G, Pietrafesa M, Pietrafesa M, et al: Differential and divergent activity of insulin‑like growth factor binding protein 6 in platinum‑sensitive versus platinum‑resistant high‑grade serous ovarian carcinoma cell lines. Oncol Lett 23: 185, 2022
APA
Piscazzi, A., Condelli, V., Crispo, F., Coda, A.R., Calice, G., Bruno, G. ... Landriscina, M. (2022). Differential and divergent activity of insulin‑like growth factor binding protein 6 in platinum‑sensitive versus platinum‑resistant high‑grade serous ovarian carcinoma cell lines. Oncology Letters, 23, 185. https://doi.org/10.3892/ol.2022.13305
MLA
Piscazzi, A., Condelli, V., Crispo, F., Coda, A. R., Calice, G., Bruno, G., Venuto, S., Tibullo, D., Giordano, G., Pietrafesa, M., Liso, A., Landriscina, M."Differential and divergent activity of insulin‑like growth factor binding protein 6 in platinum‑sensitive versus platinum‑resistant high‑grade serous ovarian carcinoma cell lines". Oncology Letters 23.6 (2022): 185.
Chicago
Piscazzi, A., Condelli, V., Crispo, F., Coda, A. R., Calice, G., Bruno, G., Venuto, S., Tibullo, D., Giordano, G., Pietrafesa, M., Liso, A., Landriscina, M."Differential and divergent activity of insulin‑like growth factor binding protein 6 in platinum‑sensitive versus platinum‑resistant high‑grade serous ovarian carcinoma cell lines". Oncology Letters 23, no. 6 (2022): 185. https://doi.org/10.3892/ol.2022.13305