Abstract: Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumor cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumor metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumor metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to pre-metastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumor progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted pre-metastatic niche formation and tumor metastasis. Our findings indicate that POSTN is essential for immunosuppressive pre-metastatic niche formation in the lungs during breast tumor metastasis and is a potential target for the prevention and treatment of breast tumor metastasis.

Link: http://dx.doi.org/10.1002/path.4747