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.
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