Osteopontin has a protective role in prostate tumor development in mice.
Osteopontin (OPN) is a protein, generally considered to play a pro-tumorigenic role, whereas several reports have demonstrated the anti-tumorigenic function of OPN during tumor development. These opposing anti- and pro-tumorigenic functions are not fully understood. Here, we report that host-derived OPN plays an anti-tumorigenic role in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model and a TRAMP tumor transplant model. Tumor suppression mediated by OPN in Rag2-/-mice suggests that OPN is dispensable in the adaptive immune response. We found that host-derived OPN enhanced infiltration of natural killer (NK) cells into TRAMP tumors. The requirement of OPN in NK cell migration towards TRAMP cells was confirmed by an ex vivo cell migration assay. In contrast to TRAMP cells, in vivo B16 tumor development was not inhibited by OPN, and B16 tumors did not show OPN-mediated cell recruitment. It is possible that low levels of chemokine expression by B16 cells do not allow OPN to enhance immune cell recruitment. In addition to demonstrating the anti-tumorigenic role of OPN in TRAMP tumor development, this study also suggests that the contribution of OPN to tumor development depends on the type of tumor as well as the source and isoform of OPN.
Department of Immunology, Duke University Medical School, Durham, NC, 27710, USA.
Keiko
K
Danzaki
Department of Immunology, Duke University Medical School, Durham, NC, 27710, USA.
Masashi
M
Kanayama
Department of Immunology, Duke University Medical School, Durham, NC, 27710, USA.
Oscar
O
Alcazar
Department of Immunology, Duke University Medical School, Durham, NC, 27710, USA. mari.shinohara@duke.edu.|Department of Molecular Genetics and Microbiology, Duke University Medical School, Durham, NC, 27710, USA. mari.shinohara@duke.edu.
Mari L
ML
Shinohara
D056704:Adaptive Immunity; D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D053495:Osteopontin / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000276:immunology*; D015398:Signal Transduction
D053495:Osteopontin
B16 cell; Cancer; Cell migration; Chemokines; NK cell; Osteopontin (OPN); TRAMP; Tumor immunology