Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo

摘要: Abstract Secreted phosphoprotein 1 (spp1), the gene encoding osteopontin (OPN), is expressed in many human carcinomas, although its vivo functions remain unclear. To delineate role of OPN during tumor progression, we have subjected null mutant mice to repeated applications a mutagen/carcinogen induce cutaneous squamous cell carcinoma. animals exhibited accelerated growth and progression had greater number metastases per animal compared with wild-type animals. However, were significantly smaller than controls. When injected into nude mice, lines same engineered reexpress spp1 recapitulated differences observed study. These inversely correlated degree macrophage infiltration. Slower-growing, OPN-producing tumors contained more macrophages, higher proportion mannose receptor positive, characteristic differentiated resting macrophages. In vitro, displayed decreased survival at clonal density lines, an observation consistent mice. Overall, provide evidence for model where host-derived acts as chemoattractant, whereas tumor-derived able inhibit function enhances or metastases.