Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases
- PMID: 10931447
Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases
Abstract
Background: Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases.
Methods: Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis.
Results: After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis.
Conclusions: Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma.
Copyright 2000 American Cancer Society.
Similar articles
-
Inhibition of vascular endothelial growth factor (VEGF) as a novel approach for cancer therapy.Medicina (B Aires). 2000;60 Suppl 2:41-7. Medicina (B Aires). 2000. PMID: 11188930
-
Effects of an antibody to vascular endothelial growth factor receptor-2 on survival, tumor vascularity, and apoptosis in a murine model of colon carcinomatosis.Int J Oncol. 2001 Feb;18(2):221-6. Int J Oncol. 2001. PMID: 11172585
-
PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration.Cancer Res. 2000 Apr 15;60(8):2178-89. Cancer Res. 2000. PMID: 10786682
-
[Role of angiogenesis in lung cancer and its metastases].Gan To Kagaku Ryoho. 1999 Dec;26(14):2131-8. Gan To Kagaku Ryoho. 1999. PMID: 10635295 Review. Japanese.
-
[Tumor progression and angiogenesis].Gan To Kagaku Ryoho. 1999 Sep;26(10):1509-19. Gan To Kagaku Ryoho. 1999. PMID: 10500543 Review. Japanese.
Cited by
-
Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines.Contemp Oncol (Pozn). 2023;27(3):198-210. doi: 10.5114/wo.2023.133742. Epub 2023 Dec 21. Contemp Oncol (Pozn). 2023. PMID: 38239861 Free PMC article.
-
Impact of ramucirumab plus erlotinib on circulating cell-free DNA from patients with untreated metastatic non-small cell lung cancer with EGFR-activating mutations (RELAY phase 3 randomized study).Transl Lung Cancer Res. 2023 Aug 30;12(8):1702-1716. doi: 10.21037/tlcr-22-736. Epub 2023 Aug 10. Transl Lung Cancer Res. 2023. PMID: 37691865 Free PMC article.
-
Early increase of plasma soluble VEGFR-2 is associated with clinical benefit from second-line treatment of paclitaxel and ramucirumab in advanced gastric cancer.Am J Cancer Res. 2022 Jul 15;12(7):3347-3356. eCollection 2022. Am J Cancer Res. 2022. PMID: 35968330 Free PMC article.
-
Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer.BMC Cancer. 2021 Oct 29;21(1):1159. doi: 10.1186/s12885-021-08890-6. BMC Cancer. 2021. PMID: 34715820 Free PMC article.
-
How May Ramucirumab Help Improve Treatment Outcome for Patients with Gastrointestinal Cancers?Cancers (Basel). 2021 Jul 15;13(14):3536. doi: 10.3390/cancers13143536. Cancers (Basel). 2021. PMID: 34298750 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Other Literature Sources
Medical
Molecular Biology Databases