IL-6 Promotes Cancer Stemness and Oncogenicity in U2OS and MG-63 Osteosarcoma Cells by Upregulating the OPN-STAT3 Pathway

Shang

Oxidative Medicine and Cellular Longevity

et al. 2020

The metastatic potential of colorectal cancer (CRC) is intensively promoted by the tumor microenvironment (TME) in a paracrine manner. As a pleiotropic inflammatory cytokine, Interleukin-6 (IL-6) is produced and involved in CRC, the same scenario where integrin αvβ6 also becomes upregulated. However, the relationship between IL-6 and integrin αvβ6 as well as their involvement in the crosstalk between CRC and TME remains largely unclear. In the present study, we demonstrated a positive correlation between the expression of IL-6 and integrin β6 in CRC samples. The mutually promotive interaction between CRC and TME was further determined by an indirect coculture system. CRC cells could augment the secretion of IL-6 from fibroblasts, which in return induced invasion and integrin β6 expression of CRC cells. Through the classic IL-6 receptor/STAT-3 signaling pathway, IL-6 mediated the upregulation of integrin β6, which was involved in the invasion and epithelial-mesenchymal transition of CRC cells induced by IL-6. Taken together, our results reveal a paracrine crosstalk between IL-6 signals originating from the TME and increased the integrin β6 level of CRC. IL-6 induces CRC invasion via upregulation of integrin β6 through the IL-6 receptor/STAT-3 signaling pathway. Combined inhibition of IL-6 along with integrin β6-targeted strategy may indicate new directions for antitumor strategies for CRC.

Section: Introductionmentioning

confidence: 99%

Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin β6 Upregulation in Colorectal Cancer

Shang

Oxidative Medicine and Cellular Longevity

et al. 2020

“…With the aim to ascertain the efficiency of the CSCs enrichment method, both qualitative and quantitative analysis were performed to characterize the sarcospheres of both MG63 and SAOS-2 cell lines, by using the 2D parental cells model as experimental control. The results provide evidences of the formation of stable sarcospheres showing in vitro spheroidal phenotype and an higher mRNA level of stemness genes OCT-4, SOX-2 and NANOG 36,54 compared to 2D parental cells (Figs. 1, 2), confirming the successful CSCs enrichment by sarcospheres formation 55,56 .…”

Section: Discussionmentioning

confidence: 73%

Scaffold-based 3D cellular models mimicking the heterogeneity of osteosarcoma stem cell niche

Bassi

Panseri

Dozio

et al. 2020

Sci Rep

The failure of the osteosarcoma conventional therapies leads to the growing need for novel therapeutic strategies. The lack of specificity for the Cancer Stem Cells (CSCs) population has been recently identified as the main limitation in the current therapies. Moreover, the traditional two-dimensional (2D) in vitro models, employed in the drug testing and screening as well as in the study of cell and molecular biology, are affected by a poor in vitro-in vivo translation ability. To overcome these limitations, this work provides two tumour engineering approaches as new tools to address osteosarcoma and improve therapy outcomes. In detail, two different hydroxyapatite-based bone-mimicking scaffolds were used to recapitulate aspects of the in vivo tumour microenvironment, focusing on CSCs niche. The biological performance of human osteosarcoma cell lines (MG63 and SAOS-2) and enriched-CSCs were deeply analysed in these complex cell culture models. The results highlight the fundamental role of the tumour microenvironment proving the mimicry of osteosarcoma stem cell niche by the use of CSCs together with the biomimetic scaffolds, compared to conventional 2D culture systems. These advanced 3D cell culture in vitro tumour models could improve the predictivity of preclinical studies and strongly enhance the clinical translation.

“…www.nature.com/scientificreports www.nature.com/scientificreports/ Zhang et al showed that interleukin 6 treatment promoted proliferation, migration, invasion, clonogenicity and chemoresistance of both MG-63 cells and U-2 OS cells. However, the same treatment did not increase any of these features in hFOB 1.19 cells 68 . Another example of a different response of MG-63 cells and hFOB 1.19 cells to the same treatment has been observed by Liu et al, revealing markedly higher sensitivity of hFOB 1.19 cells to melatonin resulting in changes in the proliferation rate 69,70 .…”

Section: Dt D1-3 Hoursmentioning

confidence: 73%

Heat treatment dependent cytotoxicity of silicalite-1 films deposited on Ti-6Al-4V alloy evaluated by bone-derived cells

Nemcakova

Jirka

Doubková

et al. 2020

Sci Rep

A silicalite-1 film (SF) deposited on Ti-6Al-4V alloy was investigated in this study as a promising coating for metallic implants. Two forms of SFs were prepared: as-synthesized SFs (SF-RT), and SFs heated up to 500 °C (SF-500) to remove the excess of template species from the SF surface. The SFs were characterized in detail by X-ray photoelectron spectroscopy (XPS), by Fourier transform infrared spectroscopy (FTIR), by scanning electron microscopy (SEM) and water contact angle measurements (WCA). Two types of bone-derived cells (hFOB 1.19 non-tumor fetal osteoblast cell line and U-2 OS osteosarcoma cell line) were used for a biocompatibility assessment. The initial adhesion of hFOB 1.19 cells, evaluated by cell numbers and cell spreading area, was better supported by SF-500 than by SF-RT. While no increase in cell membrane damage, in ROS generation and in TNF-alpha secretion of bonederived cells grown on both SFs was found, gamma H2AX staining revealed an elevated DNA damage response of U-2 OS cells grown on heat-treated samples (SF-500). This study also discusses differences between osteosarcoma cell lines and non-tumor osteoblastic cells, stressing the importance of choosing the right cell type model.