In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 8, No. 12_Supplement ( 2009-12-10), p. B175-B175
Kurzfassung:
MFG-E8/lactadherin is a secreted integrin-binding protein that promotes elimination of apoptotic cells by phagocytes leading to tolerogenic immune responses, and VEGF-induced angiogenesis, two important processes for cancer development. Here, by transcriptomic analysis of 229 biopsies of bladder carcinomas, we observed increasing expression of lactadherin with tumor progression, suggesting a protumoral role of lactadherin in this cancer. Consistently, using a mouse model of bladder carcinoma development due to carcinogen exposure, we showed that lactadherin-expressing mice developed more invasive tumors than lactadherin-deficient animals. We demonstrated that the proangiogenic function of lactadherin was not responsible for its protumoral role, since angiogenesis was similar in carcinogen-treated lactadherin-expressing or -deficient bladders, and since genes involved in VEGF-mediated angiogenesis were not co-regulated with lactadherin in human tumors. By contrast, we could ascribe the protumoral activity of lactadherin to its protolerogenic role, by showing that lactadherin expression did not promote tumor progression in mice devoid of adaptive immune system, and that lactadherin-overexpressing human tumors were invaded with immunosuppressive macrophages and regulatory T lymphocytes. Thus, lactadherin favors bladder tumor progression in human and mouse through its tolerogenic, rather than proangiogenic, function, and represents a promising therapeutic target in invasive bladder carcinomas. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B175.
Materialart:
Online-Ressource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-09-B175
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2009
ZDB Id:
2062135-8
SSG:
12
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