Purification, characterization and biological significance of tumor-derived exosomes.
Exosomes are nanovesicles that are released into the extracellular environment during the fusion of multivesicular bodies with the plasma membrane. Exosomes released from dendritic cells, dexosomes, have several biological functions, for example as immunostimulants. Some tumor cells also secrete exosomes (Tu-exosomes). Although experimental data obtained with the use of dexosomes suggest a biological function of Tu-exosomes, this still remains poorly understood. To examine the function of Tu-exosomes, we established a method for collecting highly purified Tu-exosomes, using paramagnetic beads coated with antibodies against tumor-specific proteins such as HER2/neu. With these antibody-coated beads (Ab-beads), it was possible to collect HER2-expressing Tu-exosomes of high purity. Tu-exosomes were also collected from malignant ascites, which contain exosomes secreted from various types of cells such as tumor cells, lymphoid cells and mesothelial cells. The isolation of Tu-exosomes was confirmed by FACS analysis. With regard to their biological functions, Tu-exosomes cultured with a human breast cancer cell line bound to the cell surface and increased tumor cell proliferation. These data indicate that Tu-exosomes may have physiological functions.
Koga
Kenichiro
K
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Matsumoto
Kotaro
K
Akiyoshi
Takashi
T
Kubo
Makoto
M
Yamanaka
Naoki
N
Tasaki
Akira
A
Nakashima
Hiroshi
H
Nakamura
Masafumi
M
Kuroki
Syoji
S
Tanaka
Masao
M
Katano
Mitsuo
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D022162:Cytoplasmic Vesicles / Q000737:chemistry* / Q000378:metabolism; D005089:Exocytosis; D005434:Flow Cytometry; D006801:Humans; D008854:Microscopy, Electron; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism
D018719:Erb-b2 Receptor Tyrosine Kinases