hERG1 K(+) channels regulated shedding of leukemia cell-derived microvesicles.
Summary of "hERG1 K(+) channels regulated shedding of leukemia cell-derived microvesicles."
Abstract Microvesicles (MVs) are released by various cancer cells, including leukemia cells. They can "hijack" membrane components from their parental cells and exert pleiotropic effects on tumor progression. hERG1 K(+) channels are highly expressed in cancer cells and appear of exceptional importance in favoring cancer development. Given the attributes of MVs and hERG1 K+ channels in disease progression, we investigated the putative relationship between hERG1 K(+) channels and MVs in leukemia. The protein content of MVs isolated from K562 cell supernatants were significantly higher than that from HL-60 cells. The molecular profile of these MVs showed that in addition to the myeloid lineage antigen (CD11b), MVs contained hERG1 K(+) channels. Interestingly, inhibition of hERG1 K(+) channels rapidly reduced MV fractions in supernatants. Furthermore, MVs created positive feedback loops to facilitate leukemogenesis. Exposure to MVs, the plasma membrane expression of hERG1 protein was in turn upregulated, the migration of leukemia cells was significantly increased, and the adhesion of leukemia cells to HUVECs was markedly enhanced. Importantly, hERG1 K(+) channels inhibitor E-4031 impaired these effects. We conclude that leukemia cell-derived MVs can "hijack" the plasma membrane hERG1 K(+) channels, which regulate the release of MVs and their biological effects upon leukemia cells.
Affiliation
Journal Details
This article was published in the following journal.
Name: Leukemia & lymphoma
ISSN: 1029-2403
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22292854
- DOI: http://dx.doi.org/10.3109/10428194.2012.661855
Medical and Biotech [MESH] Definitions
Voltage-dependent Anion Channels
A family of voltage-gated eukaryotic porins that form aqueous channels. They play an essential role in mitochondrial CELL MEMBRANE PERMEABILITY, are often regulated by BCL-2 PROTO-ONCOGENE PROTEINS, and have been implicated in APOPTOSIS.
Leukemia, Prolymphocytic, T-cell
A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.
Jurkat Cells
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Cell-derived Microparticles
Extracellular membrane vesicles generated by the shedding of CELL MEMBRANES blebs. Microparticles originating from PLATELETS; ENDOTHELIAL CELLS; and other cell types circulate in the peripheral blood and through the MICROVASCULATURE where larger cells cannot, functioning as active effectors in a variety of vascular processes such as INFLAMMATION; HEMOSTASIS; angiogenesis; and vascular reactivity. Increased levels are found following stimulation of bleb formation under normal or pathological conditions.
Deltaretrovirus
A genus in the family RETROVIRIDAE consisting of exogenous horizontally-transmitted viruses found in a few groups of mammals. Infections caused by these viruses include human B- or adult T-cell leukemia/lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), and bovine leukemia (ENZOOTIC BOVINE LEUKOSIS). The type species is LEUKEMIA VIRUS, BOVINE.
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