title: Interleukin-17A modulates circulating tumor cells in tumor draining vein of colorectal cancers and affects metastases.
abstract: OBJECTIVE
  Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC.
  
  
  METHODS
  CTCs were quantified using EpCAM-positive/CD45-negative immunoselection and flow cytometry in patients with CRC. A mouse model was used to investigate the mechanistic roles of CTCs and interleukin (IL)-17A in metastasis.
  
  
  RESULTS
  The number of mesenteric CTCs obtained from stage II patients was higher than that obtained from patients in stages I, III, and IV. In addition, following invasion of orthotopically implanted tumors in our mouse model, we found that CTCs exhibited an increase-then-decrease pattern, accompanied by corresponding changes in serum IL-17A levels and opposing changes in serum granulocyte macrophage colony-stimulating factor (GM-CSF) levels. Ablation of IL-17A and administration of rGM-CSF effectively suppressed the increase in CTCs and prevented metastasis in mice. Moreover, IL-17A promoted cancer cell motility, matrix digestion, and angiogenesis, whereas GM-CSF stimulated the elimination of CTCs by boosting host immunity. Notably, serum levels of IL-17A were also correlated with disease-free survival in patients with CRC.
  
  
  CONCLUSIONS
  Our results showed that CTCs and IL-17A could serve as prognostic markers and therapeutic targets for CRC metastasis. Clin Cancer Res; 20(11); 2885-97. ©2014 AACR.
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Ju-Yu
authors.initials: JY
authors.lastname: Tseng
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Chih-Yung
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Liang
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Shung-Haur
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Jen-Kou
authors.initials: JK
authors.lastname: Lin
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Yuh-Min
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
authors.forename: Jeng-Kai
authors.initials: JK
authors.lastname: Jiang
authors.affiliation: Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan linch@ym.edu.tw jkjiang@vghtpe.gov.tw.
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000401:mortality / Q000556:secondary*; D000818:Animals; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020381:Interleukin-17