title: The human complement inhibitor Sushi Domain-Containing Protein 4 (SUSD4) expression in tumor cells and infiltrating T cells is associated with better prognosis of breast cancer patients.
abstract: BACKGROUND
  The human Sushi Domain-Containing Protein 4 (SUSD4) was recently shown to function as a novel inhibitor of the complement system, but its role in tumor progression is unknown.
  
  
  METHODS
  Using immunohistochemistry and quantitative PCR, we investigated SUSD4 expression in breast cancer tissue samples from two cohorts. The effect of SUSD4 expression on cell migration and invasion was studied in vitro using two human breast cancer cell lines overexpressing SUSD4.
  
  
  RESULTS
  Tissue stainings revealed that both tumor cells and tumor-infiltrating cells expressed SUSD4. The highest SUSD4 expression was detected in differentiated tumors with decreased rate of metastasis, and SUSD4 expression was associated with improved survival of the patients. Moreover, forced SUSD4 expression in human breast cancer cells attenuated their migratory and invasive traits in culture. SUSD4 expression also inhibited colony formation of human breast cancer cells cultured on carcinoma-associated fibroblasts. Furthermore, large numbers of SUSD4-expressing T cells in the tumor stroma associated with better overall survival of the breast cancer patients.
  
  
  CONCLUSIONS
  Our findings indicate that SUSD4 expression in both breast cancer cells and T cells infiltrating the tumor-associated stroma is useful to predict better prognosis of breast cancer patients.
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Inga Maria Nilssons gata 53, 20502, Malmö, Sweden. emelie.englund@med.lu.se.
authors.forename: Emelie
authors.initials: E
authors.lastname: Englund
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Inga Maria Nilssons gata 53, 20502, Malmö, Sweden. bart.reitsma@med.lu.se.
authors.forename: Bart
authors.initials: B
authors.lastname: Reitsma
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Inga Maria Nilssons gata 53, 20502, Malmö, Sweden. ben.king@med.lu.se.
authors.forename: Ben C
authors.initials: BC
authors.lastname: King
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Inga Maria Nilssons gata 53, 20502, Malmö, Sweden. astrid.escudero_esparza@med.lu.se.
authors.forename: Astrid
authors.initials: A
authors.lastname: Escudero-Esparza
authors.affiliation: Cardiff's China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff, UK. owenS15@cardiff.ac.uk.
authors.forename: Sioned
authors.initials: S
authors.lastname: Owen
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan. aorimo@juntendo.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Orimo
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Inga Maria Nilssons gata 53, 20502, Malmö, Sweden. marcin.okroj@med.lu.se.|Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology UG‑MUG, Medical University of Gdańsk, 80210, Gdańsk, Poland. marcin.okroj@med.lu.se.
authors.forename: Marcin
authors.initials: M
authors.lastname: Okroj
authors.affiliation: Department of Clinical Pathology, Skåne University Hospital, Malmö, Sweden. lola.anagnostaki@skane.se.
authors.forename: Lola
authors.initials: L
authors.lastname: Anagnostaki
authors.affiliation: Cardiff's China Medical Research Collaborative (CCMRC), Cardiff University School of Medicine, Cardiff University, Cardiff, UK. JiangW@cardiff.ac.uk.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Department of Clinical Sciences Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden. karin.jirstrom@med.lu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Department of Translational Medicine, Division of Medical Protein Chemistry, Lund University, Inga Maria Nilssons gata 53, 20502, Malmö, Sweden. anna.blom@med.lu.se.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003169:Complement Inactivator Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D003169:Complement Inactivator Proteins; D008565:Membrane Proteins; D012334:RNA, Neoplasm; C582624:SUSD4 protein, human