Article Text
Abstract
Aim and method: In this study, we explored the responsiveness of different tumour entities (colorectal carcinoma (CRC), hepatocellular carcinoma (HCC), and the murine Lewis lung carcinoma (LLC)) to angiostatic antitumour treatment with two recombinant adenoviral vectors encoding angiostatin-like molecule (AdK1-3) and endostatin (Adendo).
Results: AdK1-3 and Adendo exerted inhibitory biological functions on endothelial cell proliferation, migration, and tube formation in vitro. AdK1-3 inhibited significantly endothelial cell infiltration in vascular endothelial growth factor embedded Matrigel plugs in mice whereas Adendo showed only minor effects. Both AdK1-3 and Adendo induced similar antitumour effects in the LLC tumour model in immune competent C57BL/6 mice but AdK1-3 had stronger inhibitory effects in athymic mice. Furthermore, AdK1-3 inhibited tumour growth in a murine CRC and human HCC model but was ineffective in a human CRC model. In contrast, Adendo did not reduce tumour progress in either of these tumour models although AdK1-3 and Adendo effectively reduced intratumoral microvessel density in LLC tumours.
Conclusion: Our data demonstrate that angiostatic gene therapy may form a feasible strategy for the treatment of established hepatocellular carcinomas and that in vivo antitumour efficacy of angiostatic proteins is tumour specific.
- cancer gene therapy
- angiogenesis
- adenovirus
- angiostatin
- endostatin
- animal models
- CRC, colorectal carcinoma
- HCC, hepatocellular carcinoma
- LLC, Lewis lung carcinoma
- VEGF, vascular endothelial growth factor
- DMEM, Dulbecco’s modified Eagle medium
- FBS, fetal bovine serum
- HUVE, human umbilical vein endothelial
- RT-PCR, reverse transcription-polymerase chain reaction
- CM, culture medium
- BrdU, bromodeoxyuridine
- pfu, plaque forming units
- MOI, multiplicity of infection
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- CRC, colorectal carcinoma
- HCC, hepatocellular carcinoma
- LLC, Lewis lung carcinoma
- VEGF, vascular endothelial growth factor
- DMEM, Dulbecco’s modified Eagle medium
- FBS, fetal bovine serum
- HUVE, human umbilical vein endothelial
- RT-PCR, reverse transcription-polymerase chain reaction
- CM, culture medium
- BrdU, bromodeoxyuridine
- pfu, plaque forming units
- MOI, multiplicity of infection
Footnotes
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↵* Present address: Department of Internal Medicine, University Hospital Bonn, Germany