Author/Authors :
Deng، نويسنده , , Jiehui and Liu، نويسنده , , Yong and Lee، نويسنده , , Heehyoung and Herrmann، نويسنده , , Andreas and Zhang، نويسنده , , Wang and Zhang، نويسنده , , Chunyan and Shen، نويسنده , , Shudan and Priceman، نويسنده , , Saul J. and Kujawski، نويسنده , , Maciej and Pal، نويسنده , , Sumanta K. and Raubitschek، نويسنده , , Andrew and Hoon، نويسنده , , Dave S.B. and Forman، نويسنده , , Stephen and Figlin، نويسنده , , Robert A. and Liu، نويسنده , , Jie and Jove، نويسنده , , Richard and Yu، نويسنده , , Hua، نويسنده ,
Abstract :
Summary
studies underscore the importance of myeloid cells in rendering distant organs hospitable for disseminating tumor cells to colonize. However, what enables myeloid cells to have an apparently superior capacity to colonize distant organs is unclear. Here, we show that S1PR1-STAT3 upregulation in tumor cells induces factors that activate S1PR1-STAT3 in various cells in premetastatic sites, leading to premetastatic niche formation. Targeting either S1PR1 or STAT3 in myeloid cells disrupts existing premetastatic niches. S1PR1-STAT3 pathway enables myeloid cells to intravasate, prime the distant organ microenvironment and mediate sustained proliferation and survival of their own and other stromal cells at future metastatic sites. Analyzing tumor-free lymph nodes from cancer patients shows elevated myeloid infiltrates, STAT3 activity, and increased survival signal.
