CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment
The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-04-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317701631 |
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| _version_ | 1850092546859991040 |
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| author | Yan Han Chunlei Wu Jing Wang Na Liu |
| author_facet | Yan Han Chunlei Wu Jing Wang Na Liu |
| author_sort | Yan Han |
| collection | DOAJ |
| description | The major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal–regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal–regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion. |
| format | Article |
| id | doaj-art-1e24137900e94903ae7111f3fda0522e |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-1e24137900e94903ae7111f3fda0522e2025-08-20T02:42:07ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317701631CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironmentYan Han0Chunlei Wu1Jing Wang2Na Liu3Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. ChinaDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. ChinaDepartment of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. ChinaDepartment of Traditional Medical Traumatology Orthopedics, Xi’an Honghui Hospital, Xi’an, P.R. ChinaThe major cause of death in osteosarcoma is the invasion and metastasis. Better understanding of the molecular mechanism of osteosarcoma invasion is essential in developing effective tumor-suppressive therapies. Interaction between chemokine receptors plays a crucial role in regulating osteosarcoma invasion. Here, we investigated the relationship between CXCR7 and CXCR4 in osteosarcoma invasion induced by bone marrow microenvironment. Human bone marrow mesenchymal stem cells were co-cultured with osteosarcoma cells to mimic actual bone marrow microenvironment. Osteosarcoma cell invasion and CXCL12/CXCR4 activation were observed within this co-culture model. Interestingly, in this co-culture model, osteosarcoma cell invasion was not inhibited by suppressing CXCR4 expression with neutralizing antibody or specific inhibitor AMD3100. Downstream signaling extracellular signal–regulated kinase and signal transducer and activator of transcription 3 were not significantly affected by CXCR4 inhibition. However, suppressing CXCR4 led to CXCR7 upregulation. Constitutive expression of CXCR7 could maintain osteosarcoma cell invasion when CXCR4 was suppressed. Simultaneously, inhibiting CXCR4 and CXCR7 compromised osteosarcoma invasion in co-culture system and suppressed extracellular signal–regulated kinase and signal transducer and activator of transcription 3 signals. Moreover, bone marrow microenvironment, not CXCL12 alone, is required for CXCR7 activation after CXCR4 suppression. Taken together, suppressing CXCR4 is not enough to impede osteosarcoma invasion in bone marrow microenvironment since CXCR7 is activated to sustain invasion. Therefore, inhibiting both CXCR4 and CXCR7 could be a promising strategy in controlling osteosarcoma invasion.https://doi.org/10.1177/1010428317701631 |
| spellingShingle | Yan Han Chunlei Wu Jing Wang Na Liu CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment Tumor Biology |
| title | CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment |
| title_full | CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment |
| title_fullStr | CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment |
| title_full_unstemmed | CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment |
| title_short | CXCR7 maintains osteosarcoma invasion after CXCR4 suppression in bone marrow microenvironment |
| title_sort | cxcr7 maintains osteosarcoma invasion after cxcr4 suppression in bone marrow microenvironment |
| url | https://doi.org/10.1177/1010428317701631 |
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