Exosomal CLIC1 released by CLL promotes HUVECs angiogenesis by regulating ITGβ1‐MAPK/ERK axis

Abstract

Accumulating evidences have suggested that exosomes are closely associated with tumor progression by affecting cell‐cell communication. Here, we aimed to investigate the roles and regulatory mechanism of exosomes released from chronic lymphocytic leukemia (CLL). The expression levels of genes and proteins in cells and exosomes were examined by quantitative real‐time PCR and Western blotting, respectively. MEC‐1 cell‐derived exosomes were obtained and co‐cultured with human umbilical vein endothelial cells (HUVECs), then the capabilities of cell proliferation, metastasis and angiogenesis of HUVECs were measured by CCK‐8, wound healing, transwell and tube formation assay, respectively. Chloride intracellular channel 1 (CLIC1) was significantly increased in CLL patients and markedly enriched in exosomes secreted by CLL cells. Exosomal CLIC1 secreted from MEC‐1 cells were successfully transferred into HUVECs and significantly promoted the phenotypes of proliferation, metastasis and angiogenesis of HUVECs. Mechanically, exosomal CLIC1 secreted from MEC‐1 cells obviously activated MAPK/ERK signaling through upregulating integrin β1 (ITGβ1) expression in HUVECs. Furthermore, rescue experiments revealed that either silencing ITGβ1 or PD98059 treatment obviously reversed the regulatory effects of exosomal CLIC1 secreted from MEC‐1 cells in HUVECs. In conclusion, CLL cell‐derived exosomes accelerated HUVECs metastasis and angiogenesis through transferring CLIC1 to regulate ITGβ1‐MAPK/ERK signaling, indicating that CLIC1 may be a therapeutic target of CLL exosomes in the tumor microenvironment.

CLIC1 Expression in Skin Biopsies from Patients With Rheumatoid and Psoriatic Arthritis as a Potential Tool to Predict Therapy Response

“…The inflammation milieu induces endothelial cell activation and triggers angiogenic processes. CLIC1 translocation in endothelial cells has been observed in malignant tumors such as glioblastoma ( 24), suggesting that it may be involved in angiogenesis, tumor progression, and metastasis (25,26). Immunohistochemical expression of CLIC1 in the tumor blood vessel endothelium has been recently reported by Raica et al (27).…”

The Innovative and Evolving Landscape of Topical Exosome and Peptide Therapies: A Systematic Review of the Available Literature

“…Topical exosomes may affect skin rejuvenation through modulation of transforming growth factor beta (TGF-B), mitogen-activated protein kinase, and extracellular signal-regulated kinase, which all play roles in cell differentiation, cellular proliferation, and apoptosis regulation. 31 , 32 Modulation of cytokines, such as TGF-B, leads to differences in extracellular matrix makeup, production of collagen, and collagenases, as well as mediates the inflammatory response to tissue damage. Increasing collagen production and modulating collagenase production can result in improved wound healing and scar formation as well as skin plumpness and elasticity.…”

Leukemia cancer cells and immune cells derived‐exosomes: Possible roles in leukemia progression and therapy

“…By transferring CLIC1 to regulate TGβ1‐MAPK/ERK signaling, CLL cell‐derived exosomes enhanced metastasis and angiogenesis. This suggests that CLIC1 could be a therapeutic target of CLL exosomes in the tumor microenvironment 71 . Exosomal eNAMPT delivery, which is involved in the metabolism of monocytes, offers a novel strategy for CLL patients to reverse immunosuppression 52 .…”