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2017 ; 37
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): ä Nephropedia Template TP
gab.com Text
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English Wikipedia
Secretion of interleukin-6 by bone marrow mesenchymal stem cells promotes
metastasis in hepatocellular carcinoma
#MMPMID28659496
Mi F
; Gong L
Biosci Rep
2017[Aug]; 37
(4
): ä PMID28659496
show ga
Mesenchymal stem cells (MSCs) interact with tumor cells and regulate
tumorigenesis and metastasis. As one of the important components of the tumor
microenvironment, MSC-secreted cytokines play a critical role in cancer
development. However, whether and how bone marrow MSCs (BMSCs) and their secreted
cytokines participate in hepatocellular carcinoma (HCC) progression, still
remains largely unknown. In the present study, we first measured the
concentration of interleukin-6 (IL-6) in BMSC conditioned medium (BMSC-CM). Next,
we assessed the changes of invasion ability in response to treatment of BMSC-CM
or recombinant IL-6 in two human HCC cell lines Bel-7404 and HepG2. Then we
analyzed the level of key components of the IL-6 signal pathway, including IL-6
receptor and signal transducer (i.e. IL-6R and gp130), a transcription factor
STAT3 (signal transducer and activator of transcription 3), as well as its target
genes BCL2, CCND1, MCL1 and MMP2, in BMSC-CM or recombinant IL-6 treated Bel-7404
and HepG2 cells. Results showed that a considerable amount of IL-6 was secreted
by BMSCs, and BMSC-CM markedly elevated Bel-7404 cell invasion rate and
stimulated the signal transduction of IL-6/STAT3 pathway. Neutralizing the
secreted IL-6 bioactivity by the anti-IL-6 antibody diminished the
invasion-promoting effect and down-regulated IL-6/STAT3 pathway of BMSC-CM
treated Bel-7404 cells. In conclusion, we found that BMSCs may activate the
IL-6/STAT3 signaling pathway and promote cell invasion in Bel-7404 cells,
suggesting that this protumor effect should be seriously considered before
clinical application of MSC-mediated cancer therapy.