Details

Autor(en) / Beteiligte

• Ucci, Argia
• Cappariello, Alfredo
• Ponzetti, Marco
• Tennant, Fabianna
• Loftus, Alexander Eamonn Patrick
• Shefferd, Kirsty
• Maurizi, Antonio
• Delle Monache, Simona
• Teti, Anna
• Rucci, Nadia

Titel

Anti-osteoblastogenic, pro-inflammatory and pro-angiogenic effect of extracellular vesicles isolated from the human osteosarcoma cell line MNNG/HOS

Ist Teil von

• Bone (New York, N.Y.), 2021-12, Vol.153, p.116130-116130, Article 116130

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2021

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Extracellular Vesicles (EVs) are becoming increasingly recognized as integral signaling vehicles in several types of cancers, including bone malignancies. However, the specific mechanisms by which EVs influence osteosarcoma progression have not been fully determined. We evaluated the effects of EVs derived from the human osteosarcoma cell line MNNG/HOS (MNNG/HOS-EVs) on bone resident cells. We found that MNNG/HOS-EVs are internalized by osteoblasts and osteoclasts in vitro, with potent inhibitory effects on osteoblast metabolic activity, cell density and alkaline phosphatase activity. Consistently, MNNG/HOS-EVs reduced the expression of cell cycle and pro-osteoblastogenic genes, whilst increasing transcriptional expression and protein release of pro-osteoclastogenic/inflammatory cytokines (RankL, Il1b, Il6 and Lcn2), pro-tumoral cytokines (CCL2,5,6,12 and CXCL1,2,5) and the metalloproteinase MMP3. MNNG/HOS-EVs did not induce osteoclast differentiation, while promoting in vitro and in vivo angiogenesis. Intriguingly, EVs derived from another osteosarcoma cell line (U2OS) reduced ALP activity but had no other effect on osteoblast phenotype. MNNG/HOS-EVs were also found to dramatically increase Serpin b2 expression in osteoblasts. To evaluate the significance of this finding, osteoblasts were forced to overexpress Serpin b2, which however did not affect osteoblast differentiation, while Il6 and Lcn2 mRNAs were up regulated. Overall, we shed light on the interactions of osteosarcoma EVs with the cells of the bone microenvironment, identifying key anti-osteoblastogenic, pro-inflammatory and pro-angiogenic factors that could contribute to osteosarcoma expansion. •Extracellular vesicles (EVs) from MNNG/HOS osteosarcoma carry bone-related mRNAs.•EVs from MNNG/HOS are up taken by osteoblasts and osteoclasts.•EVs from MNNG/HOS reduce osteoblast viability and activity.•EVs from MNNG/HOS increase TRAcP-positive area but not osteoclastogenesis.•EVs from MNNG/HOS increase in vitro and in vivo angiogenesis.