Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling
Field cancerization involves the lateral spread of premalignant or malignant disease and contributes to the recurrence of head and neck tumors. The overall hypothesis underlying this work is that endothelial cells actively participate in tumor cell invasion by secreting chemokines and creating a che...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-02-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608800590 |
| _version_ | 1818485233409851392 |
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| author | Kristy A. Warner Marta Miyazawa Mabel M.R. Cordeiro William J. Love Matthew S. Pinsky Kathleen G. Neiva Aaron C. Spalding Nör Jacques E |
| author_facet | Kristy A. Warner Marta Miyazawa Mabel M.R. Cordeiro William J. Love Matthew S. Pinsky Kathleen G. Neiva Aaron C. Spalding Nör Jacques E |
| author_sort | Kristy A. Warner |
| collection | DOAJ |
| description | Field cancerization involves the lateral spread of premalignant or malignant disease and contributes to the recurrence of head and neck tumors. The overall hypothesis underlying this work is that endothelial cells actively participate in tumor cell invasion by secreting chemokines and creating a chemotactic gradient for tumor cells. Here we demonstrate that conditioned medium from head and neck tumor cells enhance Bcl-2 expression in neovascular endothelial cells. Oral squamous cell carcinoma-3 (OSCC3) and Kaposi's sarcoma (SLK) show enhanced invasiveness when cocultured with pools of human dermal microvascular endothelial cells stably expressing Bcl-2 (HDMEC-Bcl-2), compared to cocultures with empty vector controls (HDMEC-LXSN). Xenografted OSCC3 tumors vascularized with HDMEC-Bcl-2 presented higher local invasion than OSCC3 tumors vascularized with control HDMEC-LXSN. CXCL1 and CXCL8 were upregulated in primary endothelial cells exposed to vascular endothelial growth factor (VEGF), as well as in HDMEC-Bcl-2. Notably, blockade of CXCR2 signaling, but not CXCR1, inhibited OSCC3 and SLK invasion toward endothelial cells. These data demonstrate that CXC chemokines secreted by endothelial cells induce tumor cell invasion and suggest that the process of lateral spread of tumor cells observed in field cancerization is guided by chemotactic signals that originated from endothelial cells. |
| first_indexed | 2024-12-10T16:05:50Z |
| format | Article |
| id | doaj.art-cc5d6393be7d41558dc6aa3d53f21ac3 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-10T16:05:50Z |
| publishDate | 2008-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-cc5d6393be7d41558dc6aa3d53f21ac32022-12-22T01:42:15ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-02-0110213113910.1593/neo.07815Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine SignalingKristy A. Warner0Marta Miyazawa1Mabel M.R. Cordeiro2William J. Love3Matthew S. Pinsky4Kathleen G. Neiva5Aaron C. Spalding6Nör Jacques E7Angiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USAAngiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USAAngiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USAAngiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USAAngiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USAAngiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USADepartment of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, 48109-1078, USAAngiogenesis Research Laboratory, Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, 48109-1078, USAField cancerization involves the lateral spread of premalignant or malignant disease and contributes to the recurrence of head and neck tumors. The overall hypothesis underlying this work is that endothelial cells actively participate in tumor cell invasion by secreting chemokines and creating a chemotactic gradient for tumor cells. Here we demonstrate that conditioned medium from head and neck tumor cells enhance Bcl-2 expression in neovascular endothelial cells. Oral squamous cell carcinoma-3 (OSCC3) and Kaposi's sarcoma (SLK) show enhanced invasiveness when cocultured with pools of human dermal microvascular endothelial cells stably expressing Bcl-2 (HDMEC-Bcl-2), compared to cocultures with empty vector controls (HDMEC-LXSN). Xenografted OSCC3 tumors vascularized with HDMEC-Bcl-2 presented higher local invasion than OSCC3 tumors vascularized with control HDMEC-LXSN. CXCL1 and CXCL8 were upregulated in primary endothelial cells exposed to vascular endothelial growth factor (VEGF), as well as in HDMEC-Bcl-2. Notably, blockade of CXCR2 signaling, but not CXCR1, inhibited OSCC3 and SLK invasion toward endothelial cells. These data demonstrate that CXC chemokines secreted by endothelial cells induce tumor cell invasion and suggest that the process of lateral spread of tumor cells observed in field cancerization is guided by chemotactic signals that originated from endothelial cells.http://www.sciencedirect.com/science/article/pii/S1476558608800590 |
| spellingShingle | Kristy A. Warner Marta Miyazawa Mabel M.R. Cordeiro William J. Love Matthew S. Pinsky Kathleen G. Neiva Aaron C. Spalding Nör Jacques E Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling Neoplasia: An International Journal for Oncology Research |
| title | Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling |
| title_full | Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling |
| title_fullStr | Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling |
| title_full_unstemmed | Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling |
| title_short | Endothelial Cells Enhance Tumor Cell Invasion through a Crosstalk Mediated by CXC Chemokine Signaling |
| title_sort | endothelial cells enhance tumor cell invasion through a crosstalk mediated by cxc chemokine signaling |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608800590 |
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