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Increased Expression of Pdgfa and Raf1 in Tumor-Derived Exosomes in Human Colorectal Cancer Publisher Pubmed



Vafaei S1, 2, 3 ; Gao Y4 ; Naseri M1, 2 ; Zoller M5 ; Zanjani LS1 ; Karamzadeh R3 ; Amoli HA6 ; Ebrahimi M3 ; Madjd Z1, 2
Authors
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Authors Affiliations
  1. 1. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  4. 4. Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, Hangzhou, 310016, China
  5. 5. Section Pancreas Research, University Hospital of Surgery, Heidelberg, Germany
  6. 6. Department of Surgery, Tehran University of Medical Sciences, Sina Trauma and Surgery Research Center, Tehran, Iran

Source: Cellular and Molecular Biology Published:2025


Abstract

The overexpression of tumor markers within Extracellular Vesicles (EVs), particularly in tumor-derived exosomes (TDEs), plays a pivotal role in metastasis in the context of colorectal cancer (CRC). Nonetheless, the precise role of EV content in CRC diagnosis and prognosis necessitates extensive validation through bioinformatics and clinical investigations. We explored molecular markers shared between TDEs and circulating tumor cells (CTCs) in the blood of cancer patients to identify candidate genes involved in metastasis. Common markers were analyzed in gene expression profiles of two studies (GSE31023 and GSE72577). The expression of candidate genes was assessed by RT-PCR in CTC, TDEs, and microvesicles (MVs), and was correlated with clinicopathological features. To further confirm, the expression of candidate genes was investigated in exosomes derived from the parental HT-29 colorectal cancer cell line (HT-29-EXOs), and cancer stem cells (CSCs) -enriched spheroids (CSC-EXOs) derived thereof. Gene ontology (GO) analysis suggested platelet-derived growth factor A (PDGFA) and proto-oncogene, Serine/Threonine kinase Raf-1 (RAF1) as new CRC candidate markers in CTCs and TDEs. Expression of PDGFA (P=0.0086) and RAF1 (P=0.048) were upregulated in TDEs but significantly decreased (P=0.0001) in MVs. Furthermore, expression in CSC-EXOs (P=0.0004) was increased compared to HT-29-EXOs. PDGFA and RAF1 mRNA are higher in CSC-EXOs than in HT-29-EXOs, which correlates with higher expression in CSC than in the primary tumor. Notably, as no increase was observed in MVs, PDGFA and RAF1 mRNA appear to be actively recruited into TDE. © 2025 Cellular and Molecular Biology Association. All rights reserved.
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