Research Paper|Volume 12, Issue 2|pp 1928—1951

Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics

Andrea Antonosante¹, Laura Brandolini², Michele d’Angelo¹, Elisabetta Benedetti¹, Vanessa Castelli¹, Mattia Del Maestro³, Sabino Luzzi³, Antonio Giordano^4,⁵, Annamaria Cimini^1,⁵, Marcello Allegretti²

¹Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
²Dompé Farmaceutici SpA, L’Aquila, Italy
³San Matteo Hospital, University of Pavia, Pavia, Italy
⁴Department of Medical Biotechnologies, University of Siena, Siena, Italy
⁵Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA

* Equal contribution

Received: November 4, 2019Accepted: January 2, 2020Published: January 27, 2020

https://doi.org/10.18632/aging.102733

Copyright: © 2020 Antonosante et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Glioblastoma (GB) is the most representative form of primary malignant brain tumour. Several studies indicated a pleiotropic role of CXCL8 in cancer due to its ability to modulate the tumour microenvironment, growth and aggressiveness of tumour cell. Previous studies indicated that CXCL8 by its receptors (CXCR1 and CXCR2) induced activation of the PI3K/p-Akt pathway, a crucial event in the regulation of cytoskeleton rearrangement and cell mobilization. Human GB primary cell culture and U-87MG cell line were used to study the effects of CXCR1 and CXCR2 blockage, by a dual allosteric antagonist, on cell migration and cytoskeletal dynamics. The data obtained point towards a specific effect of autocrine CXCL8 signalling on GB cell invasiveness by the activation of pathways involved in cell migration and cytoskeletal dynamics, such as PI3K/p-Akt/p-FAK, p-cortactin, RhoA, Cdc42, Acetylated α-tubulin and MMP2. All the data obtained support the concept that autocrine CXCL8 signalling plays a key role in the activation of an aggressive phenotype in primary glioblastoma cells and U-87MG cell line. These results provide new insights about the potential of a pharmacological approach targeting CXCR1/CXCR2 pathways to decrease migration and invasion of GB cells in the brain parenchyma, one of the principal mechanisms of recurrence.