Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts

American Journal of Pathology

Volumn 165, Issue 1, 2004, Pages 35-52

  Inai, Tetsuichiro ^a,e   Mancuso, Michael ^a   Hashizume, Hiroya ^b   Baffert, Fabienne ^a   Haskell, Amy ^a   Baluk, Peter ^a   Hu Lowe, Dana D ^c   Shalinsky, David R ^c   Thurston, Gavin ^d   Yancopoulos, George D ^d   McDonald, Donald M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NIIGATA UNIVERSITY GRADUATE SCHOOL OF MEDICAL AND DENTAL SCIENCES   (Japan)

^c PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^d REGENERON PHARMACEUTICALS INC   (United States)

^e KYUSHU UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS INHIBITOR; AXITINIB; UNCLASSIFIED DRUG; VASCULOTROPIN; VASCULOTROPIN TRAP;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BASEMENT MEMBRANE; BLOOD FLOW; CANCER THERAPY; CONTROLLED STUDY; ENDOTHELIUM CELL; FENESTRATION; LEWIS CARCINOMA; MOUSE; NONHUMAN; PANCREAS ISLET CELL TUMOR; PERICYTE; PHENOTYPE; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; TUMOR VASCULARIZATION;

EID: 3042548695     PISSN: 00029440     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0002-9440(10)63273-7     Document Type: Article

References (53)

1. Hlatky L, Hahnfeldt P, Folkman J: Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us. J Natl Cancer Inst 2002, 94:883-893
2. Herbst RS, Mullani NA, Davis DW, Hess KR, McConkey DJ, Charnsangavej C, O'Reilly MS, Kim HW, Baker C, Roach J, Ellis LM, Rashid A, Pluda J, Bucana C, Madden TL, Tran HT, Abbruzzese JL: Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. J Clin Oncol 2002, 20:3804-3814
3. Ellis LM: Antiangiogenic therapy: more promise and, yet again, more questions. J Clin Oncol 2003, 21:3897-3899
4. McCarthy M: Antiangiogenesis drug promising for metastatic colorectal cancer. Lancet 2003, 361:1959
5. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA: A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003, 349:427-434
6. Weidner N: Intratumor microvessel density as a prognostic factor in cancer. Am J Pathol 1995, 147:9-19
7. St. Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW: Genes expressed in human tumor endothelium. Science 2000, 289: 1197-1202
8. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, McDonald DM: Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 2000, 156: 1363-1380
9. McDonald DM, Foss AJ: Endothelial cells of tumor vessels: abnormal but not absent. Cancer Metastasis Rev 2000, 19:109-120
10. Abramsson A, Berlin O, Papayan H, Paulin D, Shani M, Betsholtz C: Analysis of mural cell recruitment to tumor vessels. Circulation 2002, 105:112-117
11. Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM: Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 2002, 160:985-1000
12. Baluk P, Morikawa S, Haskell A, Mancuso M, McDonald DM: Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors. Am J Pathol 2003, 163:1801-1815
13. Ferrara N: Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol 2002, 29:10-14
14. Ferrara N, Gerber HP, LeCouter J: The biology of VEGF and its receptors. Nat Med 2003, 9:669-676
15. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993, 362:841-844
16. Witte L, Hicklin DJ, Zhu Z, Pytowski B, Kotanides H, Rockwell P, Bohlen P: Monoclonal antibodies targeting the VEGF receptor-2(Flk1/KDR) as an anti-angiogenic therapeutic strategy. Cancer Metastasis Rev 1998, 17:155-161
17. Im SA, Gomez-Manzano C, Fueyo J, Liu TJ, Ke LD, Kim JS, Lee HY, Steck PA, Kyritsis AP, Yung WK: Antiangiogenesis treatment for gliomas: transfer of antisense-vascular endothelial growth factor inhibits tumor growth in vivo. Cancer Res 1999, 59:895-900
18. Benjamin LE, Keshet E: Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci USA 1997, 94:8761-8766
19. Goldman CK, Kendall RL, Cabrera G, Soroceanu L, Heike Y, Gillespie GY, Siegal GP, Mao X, Bett AJ, Huckle WR, Thomas KA, Curiel DT: Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate. Proc Natl Acad Sci USA 1998, 95:8795-8800
20. Davidoff AM, Leary MA, Ng CY, Vanin EF: Gene therapy-mediated expression by tumor cells of the angiogenesis inhibitor flk-1 results in inhibition of neuroblastoma growth in vivo. J Pediatr Surg 2001, 36:30-36
21. Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS: VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 2002, 99:11393-11398
22. Tseng JF, Farnebo FA, Kisker O, Becker CM, Kuo CJ, Folkman J, Mulligan RC: Adenovirus-mediated delivery of a soluble form of the VEGF receptor Flk1 delays the growth of murine and human pancreatic adenocarcinoma in mice. Surgery 2002, 132:857-865
23. Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A: Glioblastoma growth inhibited in vivo by a dominant-negative Flk-1 mutant. Nature 1994, 367:576-579
24. Fong TA, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, Ullrich A, Hirth KP, McMahon G: SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 1999, 59:99-106
25. Laird AD, Vajkoczy P, Shawver LK, Thurnher A, Liang C, Mohammadi M, Schlessinger J, Ullrich A, Hubbard SR, Blake RA, Fong TA, Strawn LM, Sun L, Tang C, Hawtin R, Tang F, Shenoy N, Hirth KP, McMahon G, Cherrington JM: SU6668 is a potent antiangiogenic and antitumor agent that induces regression of established tumors. Cancer Res 2000, 60:4152-4160
26. Drevs J, Muller-Driver R, Wittig C, Fuxius S, Esser N, Hugenschmidt H, Konerding MA, Allegrini PR, Wood J, Hennig J, Unger C, Marme D: PTK787/ZK 222584, a specific vascular endothelial growth factor-receptor tyrosine kinase inhibitor, affects the anatomy of the tumor vascular bed and the functional vascular properties as detected by dynamic enhanced magnetic resonance imaging. Cancer Res 2002, 62:4015-4022
27. Hu-Lowe D, Hallin M, Feeley R, Zou H, Rewolinski D, Wickman G, Chen E, Kim Y, Riney S, Reed J, Heller D, Simmons B, Kania R, McTigue M, Niesman M, Gregory S, Shalinsky D, Bender S: Characterization of potency and activity of the VEGF/PDGF receptor tyrosine kinase inhibitor AG013736. Proc Am Assoc Cancer Res 2002, 43: A5357
28. Yuan F, Chen Y, Dellian M, Safabakhsh N, Ferrara N, Jain RK: Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc Natl Acad Sci USA 1996, 93:14765-14770
29. Shaheen RM, Davis DW, Liu W, Zebrowski BK, Wilson MR, Bucana CD, McConkey DJ, McMahon G, Ellis LM: Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 1999, 59:5412-5416
30. Bruns CJ, Liu W, Davis DW, Shaheen RM, McConkey DJ, Wilson MR, Bucana CD, Hicklin DJ, Ellis LM: Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases. Cancer 2000, 89:488-499
31. Huang J, Frischer JS, Serur A, Kadenhe A, Yokoi A, McCrudden KW, New T, O'Toole K, Zabski S, Rudge JS, Holash J, Yancopoulos GD, Yamashiro DJ, Kandel JJ: Regression of established tumors and metastases by potent vascular endothelial growth factor blockade. Proc Natl Acad Sci USA 2003, 100:7785-7790
32. Jain RK: Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001, 7:987-989
33. Erber R, Thurnher A, Katsen AD, Groth G, Kerger H, Hammes HP, Menger MD, Ullrich A, Vajkoczy P: Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. EMBO J 2004, 18:338-340
34. Hanahan D: Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 1985, 315:115-122
35. Wickman G, Hallin M, Dillon R, Amundson K, Acena A, Grazzini M, Herrmann M, Vekich S, McTigue M, Kania R, Bender S, Shalinsky DR, Hu-Lowe DD: Further characterization of the potent VEGF/PDGF receptor tyrosine kinase inhibitor, AG013736, in preclinical tumor models for its antiangiogenesis and antitumor activity. Proc Am Assoc Cancer Res 2003, 44:A3780
36. Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D: Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003, 111:1287-1295
37. Baffert F, Thurston G, Rochon-Duck M, Le T, Brekken R, McDonald DM: Age-related changes in VEGF-dependency and angiopoietin-1 induced plasticity of adult blood vessels. Circ Res 2004, 94:984-992
38. Bergers G, Javaherian K, Lo KM, Folkman J, Hanahan D: Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science 1999, 284:808-812
39. Hashizume H, Ushiki T: Three-dimensional cytoarchitecture of angiogenic blood vessels in a gelatin sheet implanted in the rat skeletal muscular layers. Arch Histol Cytol 2002, 65:347-357
40. Roberts WG, Palade GE: Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 1995, 108:2369-2379
41. Lammert E, Gu G, McLaughlin M, Brown D, Brekken R, Murtaugh LC, Gerber HP, Ferrara N, Melton DA: Role of VEGF-A in vascularization of pancreatic islets. Curr Biol 2003, 13:1070-1074
42. Zhang W, Ran S, Sambade M, Huang X, Thorpe PE: A monoclonal antibody that blocks VEGF binding to VEGFR2 (KDR/Flk-1) inhibits vascular expression of Flk-1 and tumor growth in an orthotopic human breast cancer model. Angiogenesis 2002, 5:35-44
43. Vracko R: Basal lamina scaffold-anatomy and significance for maintenance of orderly tissue structure. Am J Pathol 1974, 77:314-346
44. Latker CH, Kuwabara T: Regression of the tunica vasculosa lentis in the postnatal rat. Invest Ophthalmol Vis Sci 1981, 21:689-699
45. Meeson A, Palmer M, Calfon M, Lang R: A relationship between apoptosis and flow during programmed capillary regression is revealed by vital analysis. Development 1996, 122:3929-3938
46. Meeson AP, Argilla M, Ko K, Witte L, Lang RA: VEGF deprivation-induced apoptosis is a component of programmed capillary regression. Development 1999, 126:1407-1415
47. Dimmeler S, Assmus B, Hermann C, Haendeler J, Zeiher AM: Fluid shear stress stimulates phosphorylation of Akt in human endothelial cells: involvement in suppression of apoptosis. Circ Res 1998, 83: 334-341
48. Hellstrom M, Gerhardt H, Kalen M, Li X, Eriksson U, Wolburg H, Betsholtz C: Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 2001, 153:543-553
49. Shaheen RM, Tseng WW, Davis DW, Liu W, Reinmuth N, Vellagas R, Wieczorek AA, Ogura Y, McConkey DJ, Drazan KE, Bucana CD, McMahon G, Ellis LM: Tyrosine kinase inhibition of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms. Cancer Res 2001, 61:1464-1468
50. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E: Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 1999, 103: 159-165
51. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D: Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2000, 2:737-744
52. Gerhardt H, Betsholtz C: Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 2003, 314:15-23
53. Fairbrother WJ, Champe MA, Christinger HW, Keyt BA, Starovasnik MA: Solution structure of the heparin-binding domain of vascular endothelial growth factor. Structure 1998, 6:637-648