The clinical significance of circulating GPC1 positive exosomes and its regulative miRNAs in colon cancer patients

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Recent study found an increased level of glypican-1 positive (GPC1 + ) plasma exosomes in patients with stage II CRC, but decreased levels of plasma miR-96-5p and miR-149. This study further investigated the clinical significance of plasma GPC1 + exosomes and plasma miR-96-5p and miR-149 levels in stage III CRC patients. To study the effect of these microRNAs on GPC1 + plasma exosomes, we isolated and purified exosomes and overexpressed human GPC1 and the microRNAs miR-96-5p and miR-149 by adenovirus vectors. Overexpression of GPC1 activated epithelial-mesenchymal transition (EMT) which then increased invasion and migration in HT29 and HCT-116 colon cancer cells. In contrast, silencing GPC1 expression and overexpressing miR-96-5p and miR-149 significantly inactivated EMT and decreased invasion and migration of HT29 and HCT-116 cells. miR-96-5p and miR-149 inhibitors significantly increased invasion and migration of HT29 and HCT-116 cells. Our results indicate that high levels of circulating GPC1 positive exosomes before and after surgery as well as low circulating miR-96-5p and miR-149 before surgery indicated a severe clinical status and poor prognosis in stage III colon cancer patients. We conclude that GPC1 can be a biomarker for relapse of stage III CRC and may be involved in EMT activation, invasion, and migration of colorectal cancer cells.

Multiple antibodies identify glypican-1 associated with exosomes from pancreatic cancer cells and serum from patients with pancreatic cancer

“…As such, exosomes from the serum of patients emerged as an attractive approach to possibly detect cancerous lesions and monitor and predict outcome of cancer patients. Several studies have reproduced our original findings related to enrichment of GPC1 in cancer exosomes, including in breast cancer exosomes, colorectal, esophageal and pancreas cancer [2][3][4][5]8,[18][19][20] (Table 1). Additionally, most of these reports show that such enrichment of GPC1 in exosomes can serve as biomarker.…”

“…In the last two years, GPC1 detection on cancer exosomes has been demonstrated by several different independent studies. Such validation included breast cancer cellsderived exosomes and colorectal and esophageal cancer-derived exosomes, in addition to exosomes analyzed from pancreatic cancer cases [2][3][4][5]8,14,[18][19][20] (Table 1). Despite employing different methodologies and approaches, GPC1 was reported as elevated in exosomes of patients with different cancer types.…”

“…Here we provide a detailed methodology, in a stepwise manner, to accompany the findings reported here ( Table 4). Collectively, 6 different antibodies have been described to identify GPC1 positive cancer exosomes by different laboratories [2][3][4][5]8,14,[18][19][20] . We look forward to a productive scientific discourse on the utility of GPC1 positive cancer exosomes in the detection of pancreatic cancer, among others.…”

Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy

“…Nevertheless, staining in EVs and during their interaction with the cellular membrane could also be identified. Recently, several scientific studies have been considering GPC1 a possible biomarker in pancreatic ductal adenocarcinoma and colorectal cancer through its detection in patients' serum exosomes [38][39][40][41][42][43][44][45]. We have first uncovered how EVs containing GPC1 are also enriched in GBM.…”

Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

“…Glypican-1 detected in exosomes was suggested as a putative biomarker for early detection of pancreatic (149)(150)(151)(152)(153)(154) and colorectal cancer (155,156).…”