scholarly journals Analysis of the signal cross talk via CCL26 in the tumor microenvironment in osteosarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masanori Kawano ◽  
Tatsuya Iwasaki ◽  
Ichiro Itonaga ◽  
Yuta Kubota ◽  
Kazuhiro Tanaka ◽  
...  

AbstractInteraction with surrounding healthy cells plays a major role in the growth and metastasis of osteosarcoma. In this study, we hypothesized that humoral factors, which do not require direct contact with cells, are involved in the interaction between osteosarcoma and the surrounding cells. We identified the humoral factor involved in the association between tumor cells and surrounding normal cells using a co-culture model and investigated the significance of our findings. When human osteosarcoma cells (MG63) and human mesenchymal stem cells (hMSCs) were co-cultured and comprehensively analyzed for changes in each culture group, we found that the expression of chemokine (CC motif) ligand 26 (CCL26) was significantly enhanced. We also analyzed the changes in cell proliferation in co-culture, enhanced interaction with administration of recombinant CCL26 (rCCL26), reduced interaction with administration of anti-CCL26 antibodies, changes in invasive and metastatic abilities. CCL26 levels, motility, and invasive capability increased in the co-culture group and the group with added rCCL26, compared to the corresponding values in the MG63 single culture group. In the group with added CCL26 neutralizing antibodies, CCL26 level decreased in both the single and co-culture groups, and motility and invasive ability were also reduced. In a nude mice lung metastasis model, the number of lung metastases increased in the co-culture group and the group with added rCCL26, whereas the number of tumors were suppressed in the group with added neutralizing antibodies compared to those in the MG63 alone. This study identified a possible mechanism by which osteosarcoma cells altered the properties of normal cells to favorably change the microenvironment proximal to tumors and to promote distant metastasis.

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 459 ◽  
Author(s):  
Chia-Chia Chao ◽  
Chiang-Wen Lee ◽  
Tsung-Ming Chang ◽  
Po-Chun Chen ◽  
Ju-Fang Liu

Osteosarcoma, the most common of all bone malignancies, has a high likelihood of lung metastasis. Up until now, the molecular mechanisms involved in osteosarcomas with lung metastases are not clearly understood. Recent observations have shown that the chemokine CXCL1 and its receptor CXCR2 assist with the homing of neutrophils into the tumor microenvironment. Here, we show that the CXCL1/CXCR2 paracrine axis is crucial for lung metastasis in osteosarcoma. In an in vivo lung metastasis model of osteosarcoma, lung blood vessels expressed CXCL1 and osteosarcoma cells expressed the CXCR2 receptor. CXCR2 expression was higher in osteosarcoma cell lines than in normal osteoblast cells. Immunohistochemistry staining of clinical osteosarcoma specimens revealed positive correlations between CXCR2 expression and pathology stage and also vascular cell adhesion molecule 1 (VCAM-1) expression. High levels of CXCL1 secreted by human pulmonary artery endothelial cells (HPAECs) promoted osteosarcoma cell mobility, which was mediated by the upregulation of VCAM-1 expression. When HPAECs-conditioned media was incubated in osteosarcoma cells, we observed that the CXCR2 receptor and FAK/PI3K/Akt/NF-κB signaling cascade were required for VCAM-1 expression. Our findings illustrate a molecular mechanism of lung metastasis in osteosarcoma and indicate that CXCL1/CXCR2 is worth targeting in treatment schemas.


2016 ◽  
Author(s):  
Jose M Moran ◽  
Olga Leal-Hernandez ◽  
Maria L Canal-Macias ◽  
Jesus M Lavado-Garcia ◽  
Raul Roncero-Martin ◽  
...  

2017 ◽  
Vol 17 (3) ◽  
pp. 424-433 ◽  
Author(s):  
Juan Cadavid-Vargas ◽  
Ignacio Leon ◽  
Susana Etcheverry ◽  
Eduardo Santi ◽  
Maria Torre ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Katerina Gioti ◽  
Anastasia Papachristodoulou ◽  
Dimitra Benaki ◽  
Nektarios Aligiannis ◽  
Alexios-Leandros Skaltsounis ◽  
...  

Oleuropein (OLEU) is the most distinguished phenolic compound found in olive fruit and the leaves of Olea europaea L., with several pharmacological properties, including anti-cancer actions. Adriamycin (ADR) is an anthracycline widely used as a chemotherapeutic agent, although it presents significant side effects. The aim of the present study was to investigate the effect of oleuropein alone (20 μg/mL) and in co-treatment with ADR (50 nM), in MG-63 human osteosarcoma cells. Therefore, cellular and molecular techniques, such as MTT assay, flow cytometry, real-time Polymerase Chain Reaction (PCR), western blot and Elisa method, as well as Nuclear Magnetic Resonance (NMR) spectroscopy, were applied to unveil changes in the signal transduction pathways involved in osteosarcoma cells survival. The observed alterations in gene, protein and metabolite levels denote that OLEU not only inhibits MG-63 cells proliferation and potentiates ADR’s cytotoxicity, but also exerts its action, at least in part, through the induction of autophagy.


2016 ◽  
Vol 49 (5) ◽  
pp. 1973-1982 ◽  
Author(s):  
Ran-Xi Zhang ◽  
Yang Li ◽  
Dong-Dong Tian ◽  
Yang Liu ◽  
Wu Nian ◽  
...  

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