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Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition
but Apoptosis in Human Proximal Tubular (HK-2) Cells: Implications for Renal
Impairment in Multiple Myeloma
#MMPMID28264449
Zhao A
; Kong F
; Liu CJ
; Yan G
; Gao F
; Guo H
; Guo AY
; Chen Z
; Li Q
Int J Mol Sci
2017[Feb]; 18
(3
): ? PMID28264449
show ga
Renal impairment (RI) is one of the hallmarks of multiple myeloma (MM) and
carries a poor prognosis. Microvesicles (MVs) are membrane vesicles and play an
important role in disease progression. Here, we investigated the role of MVs
derived from MM cells (MM-MVs) in RI of MM. We found that MM-MVs significantly
inhibited viability and induced apoptosis, but not epithelial-mesenchymal
transition in human kidney-2 (HK-2), a human renal tubular epithelial cell line.
The protein levels of cleaved caspase-3, 8, and 9, and E-cadherin, were
increased, but vementin levels were decreased in the HK-2 cells treated with
MM-MVs. Through a comparative sequencing and analysis of RNA content between the
MVs from RPMI8226 MM cells (RPMI8226-MVs) and K562 leukemia cells, RPMI8226-MVs
were enriched with more renal-pathogenic miRNAs, in which the selective miRNAs
may participate in the up-regulation of the levels of cleaved caspase-3.
Furthermore, the levels of CD138+ circulating MVs (cirMVs) in the peripheral
blood were positively correlated with the severity of RI in newly-diagnosed MM.
Our study supports MM-MVs representing a previously undescribed factor and
playing a potential role in the development of RI of MM patients, and sheds light
on the potential application of CD138+ cirMV counts in precise diagnosis of RI in
MM and exploring MM-MVs as a therapeutic target.
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