title: Tumor-associated macrophage-derived CXCL8 could induce ERα suppression via HOXB13 in endometrial cancer.
abstract: To elucidate the role of tumor-associated macrophage (TAM) in the loss of ERα in endometrial cancer (EC) and the underlying mechanism.
  
  
  
  Tissue microarrays and immunohistochemistry assays were performed using endometrial cancer tissue along with coculture, immunofluorescence, invasion assays and ChIP-qPCR using a human endometrial cancer cell line.
  
  
  
  Compared with normal tissue, an increased number of TAM was found in EC tissue (34.0 ± 2.6 vs. 8.3 ± 1.1, respectively; p < 0.001), which may downregulate ERα (27.4%, p < 0.05 for HEC-1A and 16.9%, p < 0.05 for Ishikawa) and promote EC cell invasion (1.8-fold, p < 0.001 for HEC-1A and 2.0-fold, p < 0.001 for Ishikawa). Furthermore, we found that TAM-derived CXCL8 mediated the loss of ERα and cancer invasion via HOXB13. HOXB13 was highly expressed in the ERα-negative subtype (r = -0.204, p = 0.002) and low expression of ESR1 was associated with a poor prognosis for EC patients (log-rank p < 0.05).
  
  
  
  TAM-secreted CXCL8 downregulated the ERα expression of EC cells via HOXB13, which may be associated with cancer invasion, metastasis and poor prognosis.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Tong
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie-Qi
authors.initials: JQ
authors.lastname: Ke
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fei-Zhou
authors.initials: FZ
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: wanxiaoping@tongji.edu.cn.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wan
mesh_terms: D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D047369:Chromatin Immunoprecipitation; D018920:Coculture Techniques; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019899:Paracrine Communication; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: C508606:CXCL8 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D016209:Interleukin-8
keywords: CXCL8; Endometrial cancer; Estrogen receptor alpha; HOXB13; Macrophages