Interleukin-30/IL27p28 Shapes Prostate Cancer Stem-like Cell Behavior and Is Critical for Tumor Onset and Metastasization

Cancer Research
Carlo SorrentinoEmma Di Carlo

Abstract

Prostate cancer stem-like cells (PCSLC) are believed to be responsible for prostate cancer onset and metastasis. Autocrine and microenvironmental signals dictate PCSLC behavior and patient outcome. In prostate cancer patients, IL30/IL27p28 has been linked with tumor progression, but the mechanisms underlying this link remain mostly elusive. Here, we asked whether IL30 may favor prostate cancer progression by conditioning PCSLCs and assessed the value of blocking IL30 to suppress tumor growth. IL30 was produced by PCSLCs in human and murine prostatic intraepithelial neoplasia and displayed significant autocrine and paracrine effects. PCSLC-derived IL30 supported PCSLC viability, self-renewal and tumorigenicity, expression of inflammatory mediators and growth factors, tumor immune evasion, and regulated chemokine and chemokine receptor genes, primarily via STAT1/STAT3 signaling. IL30 overproduction by PCSLCs promoted tumor onset and development associated with increased proliferation, vascularization, and myeloid cell recruitment. Furthermore, it promoted PCSLC dissemination to lymph nodes and bone marrow by upregulating the CXCR5/CXCL13 axis, and drove metastasis to lungs through the CXCR4/CXCL12 axis. These mechanisms were dras...Continue Reading

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Citations

Oct 18, 2018·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jovani Catalan-DibeneAlbert Zlotnik
May 31, 2019·Frontiers in Oncology·Gianluca CivenniCarlo V Catapano
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Mar 6, 2019·Frontiers in Cell and Developmental Biology·Alice TurdoGiorgio Stassi
Mar 16, 2019·Frontiers in Immunology·Anna E Vilgelm, Ann Richmond
Feb 10, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam L BurrackIngunn M Stromnes
Feb 27, 2021·Clinical and Translational Medicine·Carlo SorrentinoEmma Di Carlo
May 29, 2021·Experimental & Molecular Medicine·Booki MinMatthias J Feige
Aug 8, 2021·International Journal of Molecular Sciences·Andrea AbaurreaMaria M Caffarel

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