Journal
CANCER RESEARCH
Volume 70, Issue 5, Pages 1759-1765Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-1703
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Funding
- Sankyo Foundation of Life Science
- Associazione Italiana Ricerca sul Cancro
- Association International Cancer Research
- European Community [202213, 223098, NMP3-LA-2008-214402]
- Italian Ministry of Health
- Italian Ministry of University and Research
- Cariplo Foundation
- Fondation Leducq
- Telethon Foundation
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Junctional adhesion molecule-A (JAM-A)-null dendritic cells (DCs) are more motile and effective than their wild-type counterpart in promoting contact hypersensitivity reaction. Here, we show that the growth and aggressiveness of pancreatic islet cell carcinoma induced by SV40 T antigen expression in beta cells (Rip1Tag2 mice) are significantly reduced in JAM-A-null mice. Because these tumor cells do not express JAM-A, we focused on changes in stroma reactivity. In the absence of JAM-A, tumors showed a small but significant reduction in angiogenesis and a marked increase in the immune reaction with enhanced infiltration of DCs (CD11c(+) and MHC-II+) and CD4+ and CD8(+) lymphocytes. In contrast, phagocyte number was not affected. DC capacity to produce cytokines was not significantly altered, but transmigration through JAM-A-null endothelial cells was increased as compared with JAM-A-positive endothelium. On adoptive transfer, JAM-A(-/-) DCs were recruited to tumors at slightly but significantly higher rate than JAM-A(+/+) DCs. Ablation of CD4+ and CD8+ cells with specific antibodies abrogated the inhibitory effect of JAM-A deletion on tumor growth and angiogenesis. These findings support the idea that, in the Rip1Tag2 tumor model, abrogation of JAM-A reduces cancer development by increasing antitumor immune response. Cancer Res; 70(5); 1759-65. (C)2010 AACR.
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