Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma.
Cellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kappaB (RA...
| Main Authors: | , , , , , |
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| 格式: | Journal article |
| 語言: | English |
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2007
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| _version_ | 1826293564820160512 |
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| author | Lau, Y Adamopoulos, I Sabokbar, A Giele, H Gibbons, C Athanasou, N |
| author_facet | Lau, Y Adamopoulos, I Sabokbar, A Giele, H Gibbons, C Athanasou, N |
| author_sort | Lau, Y |
| collection | OXFORD |
| description | Cellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kappaB (RANK) ligand (RANKL)-dependent and -independent mechanisms. In this study, our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing's sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. Tumour-associated macrophages were isolated from two Ewing's sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs, which were capable of carrying out lacunar resorption. This osteoclast formation was inhibited by the addition of bisphosphonates. Both Ewing's sarcoma-derived fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast formation by a contact-dependent mechanism. We also found that osteoclast differentiation occurred when Ewing's TAMs were cultured with tumour necrosis factor (TNF)-alpha in the presence of M-CSF and that TC71 Ewing's sarcoma cells stimulated osteoclast formation through the release of a soluble factor, the action of which was abolished by an antibody to TNF-alpha. These results indicate that TAMs in Ewing's sarcoma are capable of osteoclast differentiation by both RANKL-dependent and TNF-alpha-dependent mechanisms and that Ewing's sarcoma cells produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of Ewing's sarcoma. |
| first_indexed | 2024-03-07T03:32:04Z |
| format | Journal article |
| id | oxford-uuid:bb0d9cc3-bc7b-4d1b-b13d-c74ae48f7ca3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:32:04Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:bb0d9cc3-bc7b-4d1b-b13d-c74ae48f7ca32022-03-27T05:14:12ZCellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bb0d9cc3-bc7b-4d1b-b13d-c74ae48f7ca3EnglishSymplectic Elements at Oxford2007Lau, YAdamopoulos, ISabokbar, AGiele, HGibbons, CAthanasou, NCellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kappaB (RANK) ligand (RANKL)-dependent and -independent mechanisms. In this study, our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing's sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. Tumour-associated macrophages were isolated from two Ewing's sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs, which were capable of carrying out lacunar resorption. This osteoclast formation was inhibited by the addition of bisphosphonates. Both Ewing's sarcoma-derived fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast formation by a contact-dependent mechanism. We also found that osteoclast differentiation occurred when Ewing's TAMs were cultured with tumour necrosis factor (TNF)-alpha in the presence of M-CSF and that TC71 Ewing's sarcoma cells stimulated osteoclast formation through the release of a soluble factor, the action of which was abolished by an antibody to TNF-alpha. These results indicate that TAMs in Ewing's sarcoma are capable of osteoclast differentiation by both RANKL-dependent and TNF-alpha-dependent mechanisms and that Ewing's sarcoma cells produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of Ewing's sarcoma. |
| spellingShingle | Lau, Y Adamopoulos, I Sabokbar, A Giele, H Gibbons, C Athanasou, N Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma. |
| title | Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma. |
| title_full | Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma. |
| title_fullStr | Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma. |
| title_full_unstemmed | Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma. |
| title_short | Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma. |
| title_sort | cellular and humoral mechanisms of osteoclast formation in ewing s sarcoma |
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