Abstract
BackgroundSpinal 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.MethodsIn 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.ResultsOur 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.ConclusionOur 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.
Highlights
Metastasis is still the most challenging problem in cancer because there is no effective strategy [1]
Lung cancer cells induce phenotypic changes in epidural Adipose-derived mesenchymal stem cells (ADSCs) To further characterize the role of lung cancer cells in the phenotypic changes in epidural ADSCs, we treated epidural ADSCs with conditioned medium (CM) from four lung cancer cell lines, PC14, A549, H3325 and H647, and evaluated the expression of α-SMA, a marker of myofibroblasts [21, 22]
The expression of α-SMA in CM-treated ADSCs was examined by immunohistochemistry (Fig. 2a), and epidural ADSCs cultured in an untreated medium were used as controls
Summary
Metastasis is still the most challenging problem in cancer because there is no effective strategy [1]. Metastatic epidural spinal cord compression (MESCC) from spinal metastasis is a common neurological complication of advanced cancer [2]. More than 90% of MESCC from lung cancers first reach the spine by direct haematogenous metastasis, usually in the vertebral column through the Baston plexus or arterial embolization or less frequently by direct invasion or extension through the intervertebral foramina, to enter the epidural space [3, 5]. As epidural fat is the last barrier in MESCC, its role in the spinal metastasis of tumours is still unclear. 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 cancerpromoting properties that influence the tumour microenvironment; there is no research on ADSCs from epidural fat far
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