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Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells
Molecular cancer research, 2017-01, Vol.15 (1), p.78-92
Nakamura, Koji
Sawada, Kenjiro
Kinose, Yasuto
Yoshimura, Akihiko
Toda, Aska
Nakatsuka, Erika
Hashimoto, Kae
Mabuchi, Seiji
Morishige, Ken-Ichirou
Kurachi, Hirohisa
Lengyel, Ernst
Kimura, Tadashi
2017
Details
Autor(en) / Beteiligte
Nakamura, Koji
Sawada, Kenjiro
Kinose, Yasuto
Yoshimura, Akihiko
Toda, Aska
Nakatsuka, Erika
Hashimoto, Kae
Mabuchi, Seiji
Morishige, Ken-Ichirou
Kurachi, Hirohisa
Lengyel, Ernst
Kimura, Tadashi
Titel
Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells
Ist Teil von
Molecular cancer research, 2017-01, Vol.15 (1), p.78-92
Ort / Verlag
United States: American Association for Cancer Research Inc
Erscheinungsjahr
2017
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR.
Sprache
Englisch
Identifikatoren
ISSN: 1541-7786
eISSN: 1557-3125
DOI: 10.1158/1541-7786.MCR-16-0191
Titel-ID: cdi_proquest_miscellaneous_1835493005
Format
–
Schlagworte
Animals
,
Cancer
,
Carcinoma, Ovarian Epithelial
,
CD44 antigen
,
Cell Communication
,
Cell Line, Tumor
,
Cell Shape
,
Cell surface
,
Cytology
,
Down-Regulation
,
Enzyme Induction
,
Epithelial Cells - metabolism
,
Epithelial Cells - pathology
,
Epithelium - pathology
,
Exosomes
,
Exosomes - metabolism
,
Exosomes - ultrastructure
,
Female
,
Gelatinase B
,
Glycoproteins
,
Humans
,
Hyaluronan Receptors - metabolism
,
Internalization
,
Matrix Metalloproteinases - biosynthesis
,
Membrane vesicles
,
Mesenchyme
,
Metastases
,
Metastasis
,
Mice, Inbred BALB C
,
Mice, Nude
,
miRNA
,
Neoplasm Invasiveness
,
Neoplasm Metastasis
,
Neoplasms, Glandular and Epithelial
,
Omentum - pathology
,
Ovarian cancer
,
Ovarian Neoplasms - metabolism
,
Ovarian Neoplasms - pathology
,
Ovarian Neoplasms - ultrastructure
,
Peritoneum
,
Peritoneum - pathology
,
Proteins
,
Signal Transduction
,
Therapeutic targets
,
Transforming Growth Factor beta - metabolism
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