Abstract：
:Extramedullary myelopoiesis occurs commonly in tumor-bearing animals and is known to lead to accumulation of peripheral myeloid-derived suppressor cells (MDSC), which play an important role in immune escape. However, the cellular and molecular mechanisms by which tumors induce extramedullary myelopoiesis are poorly understood. In this study, we found that osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44-dependent manner through the Erk1/2-MAPK pathway. Osteopontin-mediated extramedullary myelopoiesis was directly associated with increased MDSCs in tumor-bearing hosts. More importantly, osteopontin silencing in tumor cells delayed both tumor growth and extramedullary myelopoiesis, while the same treatment did not affect tumor growth in vitro. Finally, treatment with an antibody against osteopontin inhibited tumor growth and synergized with cell-based immunotherapeutic vaccines in mediating antitumor immunity. Our findings unveil a novel immunosuppressive role for tumor-derived osteopontin and offer a rationale for its therapeutic targeting in cancer treatment.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kim EK,Jeon I,Seo H,Park YJ,Song B,Lee KA,Jang Y,Chung Y,Kang CYdoi
10.1158/0008-5472.CAN-14-1482subject
Has Abstractpub_date
2014-11-15 00:00:00pages
6705-16issue
22eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-1482journal_volume
74pub_type
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