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Epidural adipose tissue-derived mesenchymal stem cell activation induced by lung cancer cells promotes malignancy and EMT of lung cancer.

Abstract：

BACKGROUND:Spinal metastasis is a major challenge in patients with advanced lung cancer, but the mechanisms in the organotropism of metastasis are still unclear. Adipose-derived mesenchymal stem cells (ADSCs) exhibit cancer-promoting properties that influence the tumour microenvironment; however, there is no research on ADSCs from epidural fat thus far. METHODS:In this study, we isolated and identified ADSCs from epidural adipose tissue for the first time. We examined the activation of epidural ADSCs treated with lung cancer cell-conditioned medium by immunohistochemistry, western blot and qRT-PCR assays. The expression of interleukin (IL)-6 family cytokines in the supernatants of ADSCs were evaluated by enzyme-linked immunosorbent assay. The effects of epidural ADSCs on the growth and invasion of lung cancer cells were evaluated with the CCK-8 and Transwell assays. The expression of signal transducer and activator of transcription 3 (STAT3), matrix metalloprotease and epithelial-mesenchymal transition markers were measured by western blot assays. RESULTS:Our results showed that ADSCs treated with lung cancer cell-conditioned medium expressed higher levels of the myofibroblast marker α-smooth muscle actin and fibroblast activation protein than ADSCs cultured alone. Then, we found that lung cancer cells induced ADSCs to secrete high levels of IL-6 family cytokines and activate the STAT3 signalling pathway. Moreover, activated epidural ADSCs exhibited the ability to promote lung cancer cell proliferation and invasion by elevating matrix metalloprotease expression and epithelial-mesenchymal transition in cancer cells. Furthermore, blocking IL-6 can counteract the differentiation and tumour-promoting effects of ADSCs. CONCLUSION:Our results suggest that ADSCs respond to lung cancer cells and are involved in the crosstalk between primary tumours and pre-metastatic niches in epidural fat.

journal_name

Stem Cell Res Ther

journal_title

Stem cell research & therapy

authors

Wang Y,Chu Y,Ren X,Xiang H,Xi Y,Ma X,Zhu K,Guo Z,Zhou C,Zhang G,Chen B

doi

10.1186/s13287-019-1280-3

subject

Has Abstract

pub_date

2019-06-13 00:00:00

pages

168

issue

issn

1757-6512

pii

10.1186/s13287-019-1280-3

journal_volume

pub_type

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Epidural adipose tissue-derived mesenchymal stem cell activation induced by lung cancer cells promotes malignancy and EMT of lung cancer.