title: S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites.
abstract: Recent 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.
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Jiehui
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Heehyoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Shudan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Saul J
authors.initials: SJ
authors.lastname: Priceman
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kujawski
authors.affiliation: Department of Medical Oncology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Raubitschek
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA.
authors.forename: Dave S B
authors.initials: DSB
authors.lastname: Hoon
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.affiliation: Department of Hematology-Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Figlin
authors.affiliation: Department of Digestive Diseases of Huashan Hospital, Department of Immunology of Shanghai Medical School, Fudan University, Shanghai, 200040, China; Center for Translational Medicine, Zhangjiang High-Tech Park, Shanghai, 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Molecular Medicine, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Jove
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA; Center for Translational Medicine, Zhangjiang High-Tech Park, Shanghai, 201203, China. Electronic address: hyu@coh.org.
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D018899:CpG Islands; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000556:secondary; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D000081025:Sphingosine-1-Phosphate Receptors; D013997:Time Factors; D014161:Transduction, Genetic; D059016:Tumor Microenvironment; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; C556330:S1pr1 protein, mouse; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; C494087:Stat3 protein, mouse