title: CEACAM1 and hollow spheroid formation modulate the chemosensitivity of colorectal cancer to 5-fluorouracil.
abstract: OBJECTIVE
  Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) re-expressed and promoted hollow spheroid (HS) formation beyond the invasion front of colorectal cancer. The aim of the present study was to clarify whether CEACAM1 cytoplasmic domain isoform balance and HS are associated with resistance to 5-fluorouracil (5FU).
  
  
  METHODS
  Two-dimensional (D) or 3D culture systems were employed to evaluate the effects of CEACAM1 cytoplasmic isoform balance and HS formation on the chemosensitivity of colorectal cancer cells to 5FU. The risk factors for postoperative recurrence were calculated based on the presence of HS and various clinicopathological characteristics in 82 patients with Stage III colorectal cancer who had undergone curative surgery followed by 5FU-based chemotherapy.
  
  
  RESULTS
  CEACAM1-4L-transfected HT29 and CEACAM1-4L and 4S expressing parental LS174T cells had significantly higher resistance to 5FU in comparison with CEACAM1-4S- or vector control-transfected cells. In 3D culture, HS formation induced by CEACAM1-4L induced chemoresistance to 5FU, whereas the solid spheres formed in response to CEACAM1-4S were destroyed by 5FU treatment. HS was identified as an independent factor for recurrence of Stage III colorectal cancer after curative resection followed by 5FU-based chemotherapy. Kaplan-Meier survival curves demonstrated that patients with HS had lower recurrence-free survival rate.
  
  
  CONCLUSIONS
  CEACAM1 long cytoplasmic domain isoform dominance and HS formation are phenotypes associated with chemoresistance to 5FU.
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Shozo
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Junji
authors.initials: J
authors.lastname: Ieda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Mitani
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Katsunari
authors.initials: K
authors.lastname: Takifuji
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hotta
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018874:Spheroids, Cellular / Q000187:drug effects*; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D005472:Fluorouracil