release of membrane-bound vesicles and inhibition of tumor cell adhesion by the peptide neopetrosiamide a释放膜结合的囊泡和抑制肿瘤细胞粘附肽neopetrosiamide.pdfVIP

Release of Membrane-Bound Vesicles and Inhibition of Tumor Cell Adhesion by the Peptide Neopetrosiamide A 1,2 2 3,4 2,3 1 Pamela Austin , Markus Heller , David E. Williams , Lawrence P. McIntosh , A. Wayne Vogl , 2 3,4 2 1,5 Leonard J. Foster , Raymond J. Andersen , Michel Roberge , Calvin D. Roskelley * 1 Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada, 2 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada, 3 Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada, 4 Department of Earth and Ocean Sciences, University of British Columbia, Vancouver, British Columbia, Canada, 5 The Program in Breast Cancer Metastasis, University of British Columbia, Vancouver, British Columbia, Canada Abstract Background: Neopetrosiamide A (NeoA) is a 28-amino acid tricyclic peptide originally isolated from a marine sponge as a tumor cell invasion inhibitor whose mechanism of action is unknown. Methodology/Principal Findings: We show that NeoA reversibly inhibits tumor cell adhesion, disassembles focal adhesions in pre-attached cells, and decreases the level of b1 integrin subunits on the cell surface. NeoA also induces the formation of dynamic, membrane-bound protrusions on the surface of treated cells and the release of membrane-bound vesicles into the culture medium. Proteomic analysis indicates that the vesicles contain EGF and transferrin receptors as well as a number of pr