Exosomal ITGA3 interferes with non‐cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients

• DOI: 10.3402/jev.v2i0.22097
• Publication Date: 2013-12-23T10:44:14Z
• Authors: Irene V. Bijnsdorp; Albert A. Geldof; Mehrdad Lavaei; Sander R. Piersma; R. Jeroen A. van ...; Connie R. Jimenez
• Keywords: 0303 health sciences; QH573-671; integrin; prostate cancer; 6. Clean water; 3. Good health; 03 medical and health sciences; proteomics; prostate cancer; integrin; biomarker; proteomics; noncancerous cells; biomarker; Original Research Article; Cytology; non-cancerous cells

BackgroundCancer cells are able to change the protein expression and behavior of non‐cancerous surrounding cells. Exosomes, secreted by prostate cancer (PCa) cells, may have a functional role in cancer metastasis and present a promising source for protein biomarkers. The aim of the present study was to identify which proteins in exosomes can influence non‐cancerous cells, and to determine whether we can use urine exosomal proteins to identify high‐risk PCa patients.MethodExosomes were isolated by ultracentrifugation. Migration and invasion were studied by the transwell (invasion) assay. Proteomics was performed by LC‐MS/MS and identified proteins were validated by Western blotting. Cellular uptake of fluorescent labeled PKH67‐exosomes was measured by FACS.ResultsBased on comparative protein profiling by mass spectrometry‐based proteomics of LNCaP‐ and PC3‐exosomes, we selected ITGA3 and ITGB1, involved in migration/invasion, for further analyses. Inhibition of exosomal ITGA3 reduced the migration and invasion of non‐cancerous prostate epithelial cells (prEC) almost completely. Cellular uptake of exosomes by prEC was higher with PC3‐exosomes compared to LNCaP exosomes. Finally, ITGA3 and ITGB1 were more abundant in urine exosomes of metastatic patients (p<0.05), compared to benign prostate hyperplasia or PCa.ConclusionThese data indicate exosomal ITGA3 and ITGB1 may play a role in manipulating non‐cancerous surrounding cells and that measurement of ITGA3 and ITGB1 in urine exosomes has the potential to identify patients with metastatic PCa in a non‐invasive manner.