title: CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment.
abstract: White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression.
authors.affiliation: The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Chieh
authors.initials: C
authors.lastname: Tseng
authors.affiliation: The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Sirin
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Li-Ning-Tapia
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Troncoso
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Pettaway
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ward
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Marsha L
authors.initials: ML
authors.lastname: Frazier
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Logothetis
authors.affiliation: The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Mikhail G
authors.identifier: 0000-0002-3743-7869
authors.initials: MG
authors.lastname: Kolonin
mesh_terms: D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000473:pathology; D052436:Adipose Tissue, White / Q000166:cytology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D061251:Primary Cell Culture; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000150:complications / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C475829:CXCL1 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016209:Interleukin-8; D034741:RNA, Small Interfering; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B