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.
Int J Mol Sci
; 18(3)2017 Feb 27.
Article
en En
| MEDLINE
| ID: mdl-28264449
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Células Epiteliales
/
Transición Epitelial-Mesenquimal
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Túbulos Renales Proximales
/
Mieloma Múltiple
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Int J Mol Sci
Año:
2017
Tipo del documento:
Article
País de afiliación:
China