Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis

Abstract

AUTHOR CONTRIBUTIONS G.R. designed the experimental approach, performed the experimental work, analyzed the data, coordinated the project and wrote the manuscript. A.H. performed primary tumour growth and exosome education in vivo studies, cancer cell proliferation in vitro studies, cancer cell culture and exosome isolation, coordinated the project and wrote the manuscript. C.M.K. generated CEMIP overexpression, performed molecular cloning work and genetic manipulation of cancer cells, cancer cell culture and exosome isolation, coordinated the project and wrote the manuscript. I.R.M. performed brain slice ex vivo FACS analysis and exosome education in vivo studies, cancer cell culture and exosome isolation, coordinated the project, wrote and reviewed the manuscript. L.S. performed brain slice ex vivo experimental work, tissue processing and immunostaining, ex vivo and in vivo ImageJ data analysis and quantification, cancer cell invasion in vitro studies, western blot analysis, cancer cell culture and exosome isolation, and contributed to figure panel assembly. D.F. performed density gradient exosome isolation, characterization and analysis, western blot analysis, and cancer cell culture. H.S.K. and P.R.O. performed RNA sequencing data analysis. I.S. performed tissue processing and immunostaining, ex vivo and in vivo ImageJ data analysis and quantification, cancer cell culture and exosome isolation. I.C.S. performed western blot analysis and assisted in analysis of human data.

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

“…Interestingly, an investigation has revealed that CEMIP can be enclosed in exosomes involved in cancer metastasis. David Lyden and coworkers demonstrated that exosomal CEMIP protein could be delivered to distant recipient cells (brain endothelial and microglial cells) to promote vascular remodeling and cancer metastasis (60). They also found that high levels of exosomal CEMIP were related to brain metastasis progression and patient survival (60).…”

The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives

“…In particular, tumor-derived exosomes have been shown to contribute to the pre-metastatic niche. They have an organotropism for metastatic organs mediated by integrins [ 77 , 78 ] and the intravenous injections of EVs in tumor-bearing mice enhances their metastatic potential in melanoma [ 79 ], pancreatic cancer [ 80 ], and in colon cancer [ 81 ]. Like all cancer cells, NB cells release EVs in the extracellular space.…”

Immune suppressed tumor microenvironment by exosomes derived from gastric cancer cells via modulating immune functions

“…It was well documented that exosomes contain a unique repertoire of mRNAs, miRNAs and proteins [45][46][47][48] . miRNAs can be transferred from exosomes of tumor cells to immune cells to affect gene expression and cell behavior 31,49 .…”