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Publication : Plasminogen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites.

First Author  Phipps KD Year  2011
Journal  Cancer Res Volume  71
Issue  21 Pages  6676-83
PubMed ID  22042827 Mgi Jnum  J:177849
Mgi Id  MGI:5296400 Doi  10.1158/0008-5472.CAN-11-1748
Citation  Phipps KD, et al. (2011) Plasminogen Receptor S100A10 Is Essential for the Migration of Tumor-Promoting Macrophages into Tumor Sites. Cancer Res 71(21):6676-83
abstractText  Macrophages are critical drivers of tumor growth, invasion, and metastasis. Movement of macrophages into tumors requires the activity of cell surface proteases such as plasmin. In this study, we offer genetic evidence that plasminogen receptor S100A10 is essential for recruitment of macrophages to the tumor site. Growth of murine Lewis lung carcinomas or T241 fibrosarcomas was dramatically reduced in S100A10-deficient mice compared with wild-type mice. The tumor growth deficit corresponded with a decrease in macrophage density that could be rescued by intraperitoneal injection of wild-type but not S100A10-deficient macrophages. Notably, macrophages of either genotype could rescue tumor growth if they were injected into the tumor itself, establishing that S100A10 was required specifically for the migratory capability needed for tumor homing. Conversely, selective depletion of macrophages from wild-type mice phenocopied the tumor growth deficit seen in S100A10-deficient mice. Together, our findings show that S100A10 is essential and sufficient for macrophage migration to tumor sites, and they define a novel rate-limiting step in tumor progression. Cancer Res; 71(21); 6676-83. (c)2011 AACR.
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