Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and TRAIL and suppress the growth of H460 human lung cancer cells. (January 2019)

• Record Type: Journal Article
• Authors: Jung, Pil Young; Ryu, Hoon; Rhee, Ki-Jong; Hwang, Soonjae; Lee, Chang Gun; Gwon, Sun-Yeong; Kim, Jiye; Kim, Juwon; Yoo, Byung-Su; Baik, Soon Koo; Bae, Keum Seok; Eom, Young Woo
• Is Part Of: Cancer letters. Volume 440-441(2019)
• Page Start: 202
• Page End: 210
• Publication Date: 2019-01
• Subjects: Adipose tissue-derived mesenchymal stem cells -- Lung cancer -- TRAIL -- IFN-β -- Necrotic cell death; 40K-ASC-CM CM recovered from 40K-ASCs -- 7-AAD 7-aminoactinomycin D -- APC allophycocyanin -- ASCs adipose tissue-derived MSCs -- Cas caspase -- CFSE carboxyfluorescein diacetate succinimidyl ester -- CM condition medium -- DMEM Dulbecco's modified Eagle's medium -- ELISA enzyme-linked immunosorbent assay -- FBS fetal bovine serum -- H460* CFSE-labeled H460 -- HBSS Hank's Balanced Salt solution -- IFNs interferons -- mbTRAIL membrane-bound TRAIL -- MSCs mesenchymal stem cells -- MTT methylthiazolyldiphenyl-tetrazolium bromide -- PBS phosphate-buffered saline -- RT-PCR reverse transcription-polymerase chain reaction -- SD standard deviation -- sTRAIL secreted TRAIL -- TRAIL tumor necrosis factor-related apoptosis-inducing ligand; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.10.017
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Although mesenchymal stem cells (MSCs) have been reported to inhibit tumor growth, the mechanism controlling this tumor suppression function is unclear. Here, we report that high-density (40, 000 cells/cm 2 ) cultured adipose tissue-derived MSCs (40K-ASCs) expressed interferon (IFN)-β and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); we also found that serum deprivation during cell culture induced the expression of IFN-β and TRAIL. In addition, the mRNA expression of IFN-β, but not TRAIL, was increased during the washing step required for the transplantation of normal-density (5000 cells/cm 2 ) cultured ASCs (5K-ASCs). When the human lung cancer cell line H460 was co-cultured with 40K-ASCs, necrotic cell death was dramatically increased in vitro . When ASCs were injected after four washes, both 5K-ASCs and 40K-ASCs substantially reduced tumor weight in H460-derived cancer animal models. These results suggest that serum deprivation during the culture of 40K-ASCs or during the washing step of 5K-ASCs can induce IFN-β and/or TRAIL expression, ultimately leading to the tumor suppression capability of ASCs. Highlights: High-density cultured ASCs expressed IFN-β and TRAIL. Serum deprivation induced IFN-β/TRAIL expression in high-density cultured ASCs. IFN-β mRNA expression was increased during washing with phosphate-buffered saline. H460 necroptosis occurred in culture with high-density cultured ASCs. High-density cultured ASCs reduced tumor weight in murine xenograft model.