Research Paper Volume 12, Issue 2 pp 1928—1951
Autocrine CXCL8-dependent invasiveness triggers modulation of actin cytoskeletal network and cell dynamics
- 1 Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
- 2 Dompé Farmaceutici SpA, L’Aquila, Italy
- 3 San Matteo Hospital, University of Pavia, Pavia, Italy
- 4 Department of Medical Biotechnologies, University of Siena, Siena, Italy
- 5 Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, Temple University, Philadelphia, PA 19122, USA
Received: November 4, 2019 Accepted: January 2, 2020 Published: January 27, 2020
https://doi.org/10.18632/aging.102733How to Cite
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.