| First Author | Gironella M | Year | 2013 |
| Journal | Cancer Res | Volume | 73 |
| Issue | 18 | Pages | 5682-94 |
| PubMed ID | 23867474 | Mgi Jnum | J:204280 |
| Mgi Id | MGI:5532207 | Doi | 10.1158/0008-5472.CAN-12-3057 |
| Citation | Gironella M, et al. (2013) Reg3beta deficiency impairs pancreatic tumor growth by skewing macrophage polarization. Cancer Res 73(18):5682-94 |
| abstractText | The lectin Reg3beta provides crucial protection to various tissues against inflammation, a potential risk factor for pancreatic ductal adenocarcinoma. Reg3beta is also overexpressed in serum and pancreatic juice from patients with this cancer, but its function in this context remains to be elucidated. In this study, we investigated the role of Reg3beta in tumor development in an orthotopic mouse model of pancreatic cancer. Reg3beta deletion in mice drastically impaired pancreatic tumor growth, correlating with decreased angiogenesis and increased apoptosis of tumor cells. Moreover, Reg3beta deficiency resulted in an alteration of the tumoral immune microenvironment, reflected by a decrease in the M2/M1 ratio of tumor-associated macrophages and an upregulation of CD3(+) cell infiltration. Addition of Reg3beta to prestimulated RAW 264.7 or primary macrophages enhanced M2 polarization through the activation of STAT3 signaling pathway. Conditioned media from Reg3beta-M2-polarized primary macrophages inhibited apoptosis and prolonged the viability of Panc02 tumor cells. Our studies reveal a novel role for Reg3beta as a tumor promoter in pancreatic adenocarcinoma through the regulation of tumor stroma. Thus, inhibition of this protein may be a useful strategy in treatment of pancreatic cancer. |
