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BibTeX
Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype
Cancer research (Chicago, Ill.), 2016-04, Vol.76 (7), p.1770-1780
Li, Ling
Li, Chao
Wang, Shaoxin
Wang, Zhaohui
Jiang, Jian
Wang, Wei
Li, Xiaoxia
Chen, Jin
Liu, Kun
Li, Chunhua
Zhu, Guiquan
2016
Details
Autor(en) / Beteiligte
Li, Ling
Li, Chao
Wang, Shaoxin
Wang, Zhaohui
Jiang, Jian
Wang, Wei
Li, Xiaoxia
Chen, Jin
Liu, Kun
Li, Chunhua
Zhu, Guiquan
Titel
Exosomes Derived from Hypoxic Oral Squamous Cell Carcinoma Cells Deliver miR-21 to Normoxic Cells to Elicit a Prometastatic Phenotype
Ist Teil von
Cancer research (Chicago, Ill.), 2016-04, Vol.76 (7), p.1770-1780
Ort / Verlag
United States
Erscheinungsjahr
2016
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Hypoxia is a common feature of solid tumors and is associated with aggressiveness and poor patient outcomes. Exosomes, initially considered to be cellular "garbage dumpsters," are now implicated in mediating interactions with the cellular environment. However, the mechanisms underlying the association between exosomes and hypoxia during cancer progression remain poorly understood. In this study, we found that exosomes derived from hypoxic oral squamous cell carcinoma (OSCC) cells increased the migration and invasion of OSCC cells in a HIF-1α and HIF-2α-dependent manner. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we performed miRNA sequencing of normoxic and hypoxic OSCC-derived exosomes. Of the 108 miRNAs that were differentially expressed, miR-21 stood out as one of the most significantly upregulated miRNAs under hypoxic conditions. miR-21 depletion in hypoxic OSCC cells led to decreased miR-21 levels in exosomes and significantly reduced cell migration and invasion. Conversely, restoration of miR-21 expression in HIF-1α and HIF-2α-depleted exosomes rescued OSCC cell migration and invasion. Moreover, exosomal miR-21 markedly enhanced snail and vimentin expression, while significantly decreasing E-cadherin levels in OSCC cells, in vitro and in vivo Finally, circulating exosomal miR-21 levels were closely associated with HIF-1α/HIF-2α expression, T stage, and lymph node metastasis in patients with OSCC. In conclusion, our findings suggest that the hypoxic microenvironment may stimulate tumor cells to generate miR-21-rich exosomes that are delivered to normoxic cells to promote prometastatic behaviors and prompt further investigation into the therapeutic value of exosome inhibition for cancer treatment. Cancer Res; 76(7); 1770-80. ©2016 AACR.
Sprache
Englisch
Identifikatoren
ISSN: 0008-5472
eISSN: 1538-7445
DOI: 10.1158/0008-5472.can-15-1625
Titel-ID: cdi_proquest_miscellaneous_1790460911
Format
–
Schlagworte
Animals
,
Carcinoma, Squamous Cell - genetics
,
Carcinoma, Squamous Cell - pathology
,
Exosomes - metabolism
,
Female
,
Humans
,
Mice
,
Mice, Nude
,
MicroRNAs - genetics
,
MicroRNAs - metabolism
,
Middle Aged
,
Mouth Neoplasms - genetics
,
Mouth Neoplasms - pathology
,
Phenotype
,
RNA, Small Interfering - metabolism
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