Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer
The αvβ3 integrin is expressed on proliferating endothelial cells and some cancer cells, but its expression on ovarian cancer cells and its potential as a therapeutic target are unknown. In this study, expression of the αvβ3 integrin on ovarian cancer cell lines and murine endothelial cells was test...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-11-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608800231 |
| _version_ | 1811252032738164736 |
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| author | Charles N. Landen Tae-Jin Kim Yvonne G. Lin William M. Merritt Aparna A. Kamat Liz Y. Han Whitney A. Spannuth Alpa M. Nick Nicholas B. Jennnings Michael S. Kinch David Tice Anil K. Sood |
| author_facet | Charles N. Landen Tae-Jin Kim Yvonne G. Lin William M. Merritt Aparna A. Kamat Liz Y. Han Whitney A. Spannuth Alpa M. Nick Nicholas B. Jennnings Michael S. Kinch David Tice Anil K. Sood |
| author_sort | Charles N. Landen |
| collection | DOAJ |
| description | The αvβ3 integrin is expressed on proliferating endothelial cells and some cancer cells, but its expression on ovarian cancer cells and its potential as a therapeutic target are unknown. In this study, expression of the αvβ3 integrin on ovarian cancer cell lines and murine endothelial cells was tested, and the effect of a fully humanized monoclonal antibody against αvβ3, Abegrin (etaracizumab), on cell invasion, viability, tumor growth, and the Akt pathway were examined in vitro and in vivo. We found that etaracizumab recognizes αvβ3 on the ovarian cancer cell lines SKOV3ip1, HeyA8, and A2780ip2 (at low levels) but not on murine endothelial cells. Etaracizumab treatment decreased ovarian cancer proliferation and invasion. In vivo, tumor-bearing mice treated with etaracizumab alone gave variable results. There was no effect on A2780ip2 growth, but a 36% to 49% tumor weight reduction in the SKOV3ip1 and HeyA8 models was found (P < .05). However, combined etaracizumab and paclitaxel was superior to paclitaxel in the SKOV3ip1 and A2780ip2 models (by 51–73%, P < .001) but not in the HeyA8 model. Treatment with etaracizumab was then noted to decrease p-Akt and p-mTOR in SKOV3ip1, but not in HeyA8, which is Akt-independent. Tumors resected after therapy showed that etaracizumab treatment reduced the proliferating cell nuclear antigen index but not microvessel density. This study identifies tumor cell αvβ3 integrin as an attractive target and defines the Akt pathway as a predictor of response to function-blocking antibody. |
| first_indexed | 2024-04-12T16:28:49Z |
| format | Article |
| id | doaj.art-f1b1524dd8434c41b2694de3d3bf3073 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T16:28:49Z |
| publishDate | 2008-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-f1b1524dd8434c41b2694de3d3bf30732022-12-22T03:25:16ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-11-0110111259126710.1593/neo.08740Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian CancerCharles N. Landen0Tae-Jin Kim1Yvonne G. Lin2William M. Merritt3Aparna A. Kamat4Liz Y. Han5Whitney A. Spannuth6Alpa M. Nick7Nicholas B. Jennnings8Michael S. Kinch9David Tice10Anil K. Sood11Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cheil General Hospital, Kwandong University College of Medicine, Seoul, South KoreaDepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USAFunctional Genetics, 708 Quince Orchard Rd, Gaithersburg, MD 20878, USAMedImmune, Inc., 1 MedImmune Way, Gaithersburg, MD 20878, USADepartment of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler Boulevard, Unit 1362, Houston, TX 77030, USAThe αvβ3 integrin is expressed on proliferating endothelial cells and some cancer cells, but its expression on ovarian cancer cells and its potential as a therapeutic target are unknown. In this study, expression of the αvβ3 integrin on ovarian cancer cell lines and murine endothelial cells was tested, and the effect of a fully humanized monoclonal antibody against αvβ3, Abegrin (etaracizumab), on cell invasion, viability, tumor growth, and the Akt pathway were examined in vitro and in vivo. We found that etaracizumab recognizes αvβ3 on the ovarian cancer cell lines SKOV3ip1, HeyA8, and A2780ip2 (at low levels) but not on murine endothelial cells. Etaracizumab treatment decreased ovarian cancer proliferation and invasion. In vivo, tumor-bearing mice treated with etaracizumab alone gave variable results. There was no effect on A2780ip2 growth, but a 36% to 49% tumor weight reduction in the SKOV3ip1 and HeyA8 models was found (P < .05). However, combined etaracizumab and paclitaxel was superior to paclitaxel in the SKOV3ip1 and A2780ip2 models (by 51–73%, P < .001) but not in the HeyA8 model. Treatment with etaracizumab was then noted to decrease p-Akt and p-mTOR in SKOV3ip1, but not in HeyA8, which is Akt-independent. Tumors resected after therapy showed that etaracizumab treatment reduced the proliferating cell nuclear antigen index but not microvessel density. This study identifies tumor cell αvβ3 integrin as an attractive target and defines the Akt pathway as a predictor of response to function-blocking antibody.http://www.sciencedirect.com/science/article/pii/S1476558608800231 |
| spellingShingle | Charles N. Landen Tae-Jin Kim Yvonne G. Lin William M. Merritt Aparna A. Kamat Liz Y. Han Whitney A. Spannuth Alpa M. Nick Nicholas B. Jennnings Michael S. Kinch David Tice Anil K. Sood Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer Neoplasia: An International Journal for Oncology Research |
| title | Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer |
| title_full | Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer |
| title_fullStr | Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer |
| title_full_unstemmed | Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer |
| title_short | Tumor-Selective Response to Antibody-Mediated Targeting of αvβ3 Integrin in Ovarian Cancer |
| title_sort | tumor selective response to antibody mediated targeting of αvβ3 integrin in ovarian cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608800231 |
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