Analysis of heterogeneity of tumor stem cells and EMT using Crk adaptor protein

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15106
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Hokkaido University
• Principal Investigator: Tsuda Masumi 北海道大学, 医学研究科, 講師 (30431307)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: エクソソーム / CRK / 浸潤 / 転移 / 腫瘍ヘテロジェナイティ

Outline of Final Research Achievements

We unveiled a novel function of CRK adaptors via exosomes in tumor progression and metastasis in invasive bladder cancer (BC). CRK is overexpressed in invasive UM-UC-3 BC cells, and CRK knockdown downregulated the expression of ErbB2. In an orthotopic xenograft model, metastases to lung, liver, and bone of UM-UC- 3 cells were completely abolished by CRK elimination. Mass spectrometry analysis identified that ErbB2 is contained in UM-UC-3-derived exosomes, which significantly increased proliferation and invasion of low-grade 5637 BC cells and HUVECs. In athymic mice educated by UM-UC-3-derived exosomes, intravenously implanted UM-UC-3 cells developed lung metastasis with increased tumor angiogenesis, whereas exosomes with CRK depletion could not. In conclusion, CRK adaptors contribute to tumor heterogeneity of invasive BC via exosome, resulting in the tumor progression and metastasis.

Free Research Field

実験病理学