| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Reproductive Endocrinology Center,*
Department
of Obstetrics, Gynecology and Reproductive Sciences, University of
California, San Francisco, San Francisco, and Department of
Cardiovascular Research,
Genentech, Inc.,
South San Francisco, California
Ovarian cancer is characterized by the rapid growth of solid intraperitoneal tumors and large volumes of ascitic fluid. Vascular endothelial growth factor (VEGF) augments tumor growth by inducing neovascularization and may stimulate ascites formation by increasing vascular permeability. We examined the role of VEGF in ovarian carcinoma using in vivo models in which intraperitoneal or subcutaneous tumors were induced in immunodeficient mice using the human ovarian carcinoma cell line SKOV-3. After tumor engraftment (7 to 10 days), some mice were treated with a function-blocking VEGF antibody (A4.6.1) specific for human VEGF. A4.6.1 significantly (P < 0.05) inhibited subcutaneous SKOV-3 tumor growth compared with controls. However, tumor growth resumed when A4.6.1 treatment was discontinued. In mice bearing intraperitoneal tumors (IP mice), ascites production and intraperitoneal carcinomatosis were detected 3 to 7 weeks after SKOV-3 inoculation. Importantly, A4.6.1 completely inhibited ascites production in IP mice, although it only partially inhibited intraperitoneal tumor growth. Tumor burden was variable in A4.6.1-treated IP mice; some had minimal tumor, whereas in others tumor burden was similar to that of controls. When A4.6.1 treatment was stopped, IP mice rapidly (within 2 weeks) developed ascites and became cachectic. These data suggest that in ovarian cancer, tumor-derived VEGF is obligatory for ascites formation but not for intraperitoneal tumor growth. Neutralization of VEGF activity may have clinical application in inhibiting malignant ascites formation in ovarian cancer.
This article has been cited by other articles:
 |
|
 |
|
  D. Belotti, C. Calcagno, A. Garofalo, D. Caronia, E. Riccardi, R. Giavazzi, and G. Taraboletti Vascular Endothelial Growth Factor Stimulates Organ-Specific Host Matrix Metalloproteinase-9 Expression and Ovarian Cancer Invasion Mol. Cancer Res., April 1, 2008; 6(4): 525 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Vassileva, C. J. Allen, and M. Piquette-Miller Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer Mol. Cancer Ther., March 1, 2008; 7(3): 630 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-H. Jeon, C. Jang, J. Han, R. P. Kataru, L. Piao, K. Jung, H. J. Cha, R. A. Schwendener, K. Y. Jang, K.-S. Kim, et al. Profound but Dysfunctional Lymphangiogenesis via Vascular Endothelial Growth Factor Ligands from CD11b+ Macrophages in Advanced Ovarian Cancer Cancer Res., February 15, 2008; 68(4): 1100 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lu, A. A. Kamat, Y. G. Lin, W. M. Merritt, C. N. Landen, T. J. Kim, W. Spannuth, T. Arumugam, L. Y. Han, N. B. Jennings, et al. Dual Targeting of Endothelial Cells and Pericytes in Antivascular Therapy for Ovarian Carcinoma Clin. Cancer Res., July 15, 2007; 13(14): 4209 - 4217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Robinson-Smith, I. Isaacsohn, C. A. Mercer, M. Zhou, N. Van Rooijen, N. Husseinzadeh, M. M. McFarland-Mancini, and A. F. Drew Macrophages Mediate Inflammation-Enhanced Metastasis of Ovarian Tumors in Mice Cancer Res., June 15, 2007; 67(12): 5708 - 5716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hu, N. Ferrara, and R. B. Jaffe Paracrine VEGF/VE-Cadherin Action on Ovarian Cancer Permeability. Experimental Biology and Medicine, November 1, 2006; 231(10): 1646 - 1652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Narita, J. Staub, J. Chien, K. Meyer, M. Bauer, A. Friedl, S. Ramakrishnan, and V. Shridhar HSulf-1 Inhibits Angiogenesis and Tumorigenesis In vivo. Cancer Res., June 15, 2006; 66(12): 6025 - 6032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. DiFeo, G. Narla, J. Hirshfeld, O. Camacho-Vanegas, J. Narla, S. L. Rose, T. Kalir, S. Yao, A. Levine, M. J. Birrer, et al. Roles of KLF6 and KLF6-SV1 in Ovarian Cancer Progression and Intraperitoneal Dissemination. Clin. Cancer Res., June 15, 2006; 12(12): 3730 - 3739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hossein Pourgholami, Z. Yan Cai, Y. Lu, L. Wang, and D. Lawson Morris Albendazole: a Potent Inhibitor of Vascular Endothelial Growth Factor and Malignant Ascites Formation in OVCAR-3 Tumor-Bearing Nude Mice. Clin. Cancer Res., March 15, 2006; 12(6): 1928 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yasumoto, K. Koizumi, A. Kawashima, Y. Saitoh, Y. Arita, K. Shinohara, T. Minami, T. Nakayama, H. Sakurai, Y. Takahashi, et al. Role of the CXCL12/CXCR4 Axis in Peritoneal Carcinomatosis of Gastric Cancer Cancer Res., February 15, 2006; 66(4): 2181 - 2187. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kim, I.-Y. Park, J. Lim, Y. Kim, K. T. Han, W. H. Chung, and K. Han Antitumor and Normal Cell Protective Effect of PKC412 in the Athymic Mouse Model of Ovarian Cancer Ann. Clin. Lab. Sci., January 1, 2006; 36(4): 455 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Said and K. Motamed Absence of Host-Secreted Protein Acidic and Rich in Cysteine (SPARC) Augments Peritoneal Ovarian Carcinomatosis Am. J. Pathol., December 1, 2005; 167(6): 1739 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Suganuma, K. Ino, K. Shibata, H. Kajiyama, T. Nagasaka, S. Mizutani, and F. Kikkawa Functional Expression of the Angiotensin II Type1 Receptor in Human Ovarian Carcinoma Cells and Its Blockade Therapy Resulting in Suppression of Tumor Invasion, Angiogenesis, and Peritoneal Dissemination Clin. Cancer Res., April 1, 2005; 11(7): 2686 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-P. Gerber and N. Ferrara Pharmacology and Pharmacodynamics of Bevacizumab as Monotherapy or in Combination with Cytotoxic Therapy in Preclinical Studies Cancer Res., February 1, 2005; 65(3): 671 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Skinner, J. Z. Zheng, J. Fang, F. Agani, and B.-H. Jiang Vascular Endothelial Growth Factor Transcriptional Activation Is Mediated by Hypoxia-inducible Factor 1{alpha}, HDM2, and p70S6K1 in Response to Phosphatidylinositol 3-Kinase/AKT Signaling J. Biol. Chem., October 29, 2004; 279(44): 45643 - 45651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ferrara Vascular Endothelial Growth Factor: Basic Science and Clinical Progress Endocr. Rev., August 1, 2004; 25(4): 581 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Cao, J. Fang, C. Xia, X. Shi, and B.-H. Jiang trans-3,4,5'-Trihydroxystibene Inhibits Hypoxia-Inducible Factor 1{alpha} and Vascular Endothelial Growth Factor Expression in Human Ovarian Cancer Cells Clin. Cancer Res., August 1, 2004; 10(15): 5253 - 5263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fang, Z. Cao, Y. C. Chen, E. Reed, and B.-H. Jiang 9-{beta}-D-Arabinofuranosyl-2-fluoroadenine Inhibits Expression of Vascular Endothelial Growth Factor through Hypoxia-Inducible Factor-1 in Human Ovarian Cancer Cells Mol. Pharmacol., July 1, 2004; 66(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. X. Chen Expanding the Clinical Development of Bevacizumab Oncologist, June 1, 2004; 9(suppl_1): 27 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Byrne, L. Ross, J. Holash, M. Nakanishi, L. Hu, J. I. Hofmann, G. D. Yancopoulos, and R. B. Jaffe Vascular Endothelial Growth Factor-Trap Decreases Tumor Burden, Inhibits Ascites, and Causes Dramatic Vascular Remodeling in an Ovarian Cancer Model Clin. Cancer Res., November 15, 2003; 9(15): 5721 - 5728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Garofalo, E. Naumova, L. Manenti, C. Ghilardi, G. Ghisleni, M. Caniatti, T. Colombo, J. M. Cherrington, E. Scanziani, M. I. Nicoletti, et al. The Combination of the Tyrosine Kinase Receptor Inhibitor SU6668 with Paclitaxel Affects Ascites Formation and Tumor Spread in Ovarian Carcinoma Xenografts Growing Orthotopically Clin. Cancer Res., August 1, 2003; 9(9): 3476 - 3485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, N. Yang, J.-R. Conejo-Garcia, D. Katsaros, A. Mohamed-Hadley, S. Fracchioli, K. Schlienger, A. Toll, B. Levine, S. C. Rubin, et al. Expression of Endocrine Gland-derived Vascular Endothelial Growth Factor in Ovarian Carcinoma Clin. Cancer Res., January 1, 2003; 9(1): 264 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E S Bamberger and C W Perrett Angiogenesis in epithelian ovarian cancer Mol. Pathol., December 1, 2002; 55(6): 348 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, N. Yang, J.-R. Conejo Garcia, A. Mohamed, F. Benencia, S. C. Rubin, D. Allman, and G. Coukos Generation of a Syngeneic Mouse Model to Study the Effects of Vascular Endothelial Growth Factor in Ovarian Carcinoma Am. J. Pathol., December 1, 2002; 161(6): 2295 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. F. Dvorak Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy J. Clin. Oncol., November 1, 2002; 20(21): 4368 - 4380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hu, J. Hofmann, C. Zaloudek, N. Ferrara, T. Hamilton, and R. B. Jaffe Vascular Endothelial Growth Factor Immunoneutralization Plus Paclitaxel Markedly Reduces Tumor Burden and Ascites in Athymic Mouse Model of Ovarian Cancer Am. J. Pathol., November 1, 2002; 161(5): 1917 - 1924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hasumi, H. Mizukami, M. Urabe, T. Kohno, K. Takeuchi, A. Kume, M. Momoeda, H. Yoshikawa, T. Tsuruo, M. Shibuya, et al. Soluble FLT-1 Expression Suppresses Carcinomatous Ascites in Nude Mice Bearing Ovarian Cancer Cancer Res., April 1, 2002; 62(7): 2019 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hu, J. Hofmann, Y. Lu, G. B. Mills, and R. B. Jaffe Inhibition of Phosphatidylinositol 3'-Kinase Increases Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models Cancer Res., February 1, 2002; 62(4): 1087 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. A. Duyndam, M. C. G. W. Hilhorst, H. M. M. Schluper, H. M. W. Verheul, P. J. van Diest, G. Kraal, H. M. Pinedo, and E. Boven Vascular Endothelial Growth Factor-165 Overexpression Stimulates Angiogenesis and Induces Cyst Formation and Macrophage Infiltration in Human Ovarian Cancer Xenografts Am. J. Pathol., February 1, 2002; 160(2): 537 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Aslam and C. R. Marino Malignant Ascites: New Concepts in Pathophysiology, Diagnosis, and Management Arch Intern Med, December 10, 2001; 161(22): 2733 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hayashibara, Y. Yamada, T. Miyanishi, H. Mori, T. Joh, T. Maeda, N. Mori, T. Maita, S. Kamihira, and M. Tomonaga Vascular Endothelial Growth Factor and Cellular Chemotaxis: A Possible Autocrine Pathway in Adult T-Cell Leukemia Cell Invasion Clin. Cancer Res., September 1, 2001; 7(9): 2719 - 2726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Wulff, H. Wilson, J. S. Rudge, S. J. Wiegand, S. F. Lunn, and H. M. Fraser Luteal Angiogenesis: Prevention and Intervention by Treatment with Vascular Endothelial Growth Factor TrapA40 J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3377 - 3386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Folkman A New Link in Ovarian Cancer Angiogenesis: Lysophosphatidic Acid and Vascular Endothelial Growth Factor Expression J Natl Cancer Inst, May 16, 2001; 93(10): 734 - 735. [Full Text] [PDF]
|
|
|
|
|
|
Y.-L. Hu, M.-K. Tee, E. J. Goetzl, N. Auersperg, G. B. Mills, N. Ferrara, and R. B. Jaffe Lysophosphatidic Acid Induction of Vascular Endothelial Growth Factor Expression in Human Ovarian Cancer Cells J Natl Cancer Inst, May 16, 2001; 93(10): 762 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Auersperg, A. S. T. Wong, K.-C. Choi, S. K. Kang, and P. C. K. Leung Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology Endocr. Rev., April 1, 2001; 22(2): 255 - 288. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. Ivarsson, K. Sundfeldt, M. Brannstrom, P. Hellberg, and P. O. Janson Diverse effects of FSH and LH on proliferation of human ovarian surface epithelial cells Hum. Reprod., January 1, 2001; 16(1): 18 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Salani, V. Di Castro, M. R. Nicotra, L. Rosano, R. Tecce, A. Venuti, P. G. Natali, and A. Bagnato Role of Endothelin-1 in Neovascularization of Ovarian Carcinoma Am. J. Pathol., November 1, 2000; 157(5): 1537 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Brekken, J. P. Overholser, V. A. Stastny, J. Waltenberger, J. D. Minna, and P. E. Thorpe Selective Inhibition of Vascular Endothelial Growth Factor (VEGF) Receptor 2 (KDR/Flk-1) Activity by a Monoclonal Anti-VEGF Antibody Blocks Tumor Growth in Mice Cancer Res., September 1, 2000; 60(18): 5117 - 5124. [Abstract] [Full Text]
|
|
|
|
|
|
A. Saaristo, T. A. Partanen, J. Arola, L. Jussila, M. Hytonen, A. Makitie, S. Vento, A. Kaipainen, H. Malmberg, and K. Alitalo Vascular Endothelial Growth Factor-C and Its Receptor VEGFR-3 in the Nasal Mucosa and in Nasopharyngeal Tumors Am. J. Pathol., July 1, 2000; 157(1): 7 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Favoni and A. De Cupis The Role of Polypeptide Growth Factors in Human Carcinomas: New Targets for a Novel Pharmacological Approach Pharmacol. Rev., June 1, 2000; 52(2): 179 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. F. Roby, C. C. Taylor, J. P. Sweetwood, Y. Cheng, J. L. Pace, O. Tawfik, D. L. Persons, P. G. Smith, and P. F. Terranova Development of a syngeneic mouse model for events related to ovarian cancer Carcinogenesis, April 1, 2000; 21(4): 585 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.M.W. Verheul, K. Hoekman, A.S. Jorna, E.F. Smit, and H.M. Pinedo Targeting Vascular Endothelial Growth Factor Blockade: Ascites and Pleural Effusion Formation Oncologist, April 1, 2000; 5(90001): 45 - 50. [Abstract] [Full Text]
|
|
|
|
|
|
L. Hu, C. Zaloudek, G. B. Mills, J. Gray, and R. B. Jaffe In Vivo and in Vitro Ovarian Carcinoma Growth Inhibition by a Phosphatidylinositol 3-Kinase Inhibitor (LY294002) Clin. Cancer Res., March 1, 2000; 6(3): 880 - 886. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Kondo, S. Arii, A. Mori, M. Furutani, T. Chiba, and M. Imamura Enhancement of Angiogenesis, Tumor Growth, and Metastasis by Transfection of Vascular Endothelial Growth Factor into LoVo Human Colon Cancer Cell Line Clin. Cancer Res., February 1, 2000; 6(2): 622 - 630. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Thurston, C. Suri, K. Smith, J. McClain, T. N. Sato, G. D. Yancopoulos, and D. M. McDonald Leakage-Resistant Blood Vessels in Mice Transgenically Overexpressing Angiopoietin-1 Science, December 24, 1999; 286(5449): 2511 - 2514. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Aoki and G. Tosato Role of Vascular Endothelial Growth Factor/Vascular Permeability Factor in the Pathogenesis of Kaposi's Sarcoma-Associated Herpesvirus-Infected Primary Effusion Lymphomas Blood, December 15, 1999; 94(12): 4247 - 4254. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
