alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner.

Abstract:

:To define the role of the alpha2beta1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and alpha2-null mice. Our findings reveal that the alpha2beta1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F10 melanoma cells, mice lacking alpha2beta1 integrin ex-pression exhibit increased tumor angiogenesis associated with up-regulated VEGFR1 expression. In contrast, there was no alpha2beta1 integrin-dependent difference in the angiogenic response to Lewis lung carcinoma (LLC) cells. Interestingly, whereas B16F10 cells secrete high levels of placental growth factor (PLGF), LLC cells produce high levels of VEGF, but low levels of PLGF. The alpha2beta1 integrin-dependent difference in angiogenesis was restored to LLC cells by expression of PLGF, strongly suggesting that the angiogenic phenotype and tumor growth in the alpha2-null host is dependent on specific interactions between the tumor cell and the genetically defined integrin repertoire of the host microenvironment. Thus integrin alpha2-null mice represent an example of genetic alterations of "the soil" determining response to the "seed."

journal_name

Blood

journal_title

Blood

authors

Zhang Z,Ramirez NE,Yankeelov TE,Li Z,Ford LE,Qi Y,Pozzi A,Zutter MM

doi

10.1182/blood-2007-06-094680

subject

Has Abstract

pub_date

2008-02-15 00:00:00

pages

1980-8

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2007-06-094680

journal_volume

111

pub_type

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