Placental growth factor-1 attenuates vascular endothelial growth factor-A-dependent tumor angiogenesis during beta cell carcinogenesis

Schomber, Tibor; Kopfstein, Lucie; Djonov, Valentin; Albrecht, Imke; Baeriswyl, Vanessa; Strittmatter, Karin; Christofori, Gerhard (2007). Placental growth factor-1 attenuates vascular endothelial growth factor-A-dependent tumor angiogenesis during beta cell carcinogenesis. Cancer research, 67(22), pp. 10840-8. Birmingham, Ala.: American Association for Cancer Research AACR 10.1158/0008-5472CAN-07-1034

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Members of the vascular endothelial growth factor (VEGF) family are critical players in angiogenesis and lymphangiogenesis. Although VEGF-A has been shown to exert fundamental functions in physiologic and pathologic angiogenesis, the exact role of the VEGF family member placental growth factor (PlGF) in tumor angiogenesis has remained controversial. To gain insight into PlGF function during tumor angiogenesis, we have generated transgenic mouse lines expressing human PlGF-1 in the beta cells of the pancreatic islets of Langerhans (Rip1PlGF-1). In single-transgenic Rip1PlGF-1 mice, intra-insular blood vessels are found highly dilated, whereas islet physiology is unaffected. Upon crossing of these mice with the Rip1Tag2 transgenic mouse model of pancreatic beta cell carcinogenesis, tumors of double-transgenic Rip1Tag2;Rip1PlGF-1 mice display reduced growth due to attenuated tumor angiogenesis. The coexpression of transgenic PlGF-1 and endogenous VEGF-A in the beta tumor cells of double-transgenic animals causes the formation of low-angiogenic hPlGF-1/mVEGF-A heterodimers at the expense of highly angiogenic mVEGF-A homodimers resulting in diminished tumor angiogenesis and reduced tumor infiltration by neutrophils, known to contribute to the angiogenic switch in Rip1Tag2 mice. The results indicate that the ratio between the expression levels of two members of the VEGF family of angiogenic factors, PlGF-1 and VEGF-A, determines the overall angiogenic activity and, thus, the extent of tumor angiogenesis and tumor growth.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Djonov, Valentin

ISSN:

0008-5472

ISBN:

18006829

Publisher:

American Association for Cancer Research AACR

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:56

Last Modified:

10 Nov 2014 07:37

Publisher DOI:

10.1158/0008-5472CAN-07-1034

PubMed ID:

18006829

Web of Science ID:

000251044000029

URI:

https://boris.unibe.ch/id/eprint/23713 (FactScience: 43552)

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