title: Plasminogen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites.
abstract: 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.
authors: Department of Biochemistry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors: Kyle D
authors: KD
authors: Phipps
authors: Alexi P
authors: AP
authors: Surette
authors: Paul A
authors: PA
authors: O'Connell
authors: David M
authors: DM
authors: Waisman
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D018450:Disease Progression; D004789:Enzyme Activation; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology / Q000637:transplantation; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D010641:Phenotype; D010958:Plasminogen / Q000378:metabolism; D009418:S100 Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D009363:Neoplasm Proteins; D010958:Plasminogen; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10