title: P4H9-detected molecule expression on spindle-shaped fibroblasts indicates malignant phenotype of colorectal cancer.
abstract: BACKGROUND
  Our previous study using a mammary fat pad mouse model showed that P4H9, produced by the β2 integrin epitope, detected a molecule on fibroblasts in response to carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-expressing cancer cells. P4H9-detected molecule (PDM) expression appeared to be associated with myofibroblast differentiation. In this study, we investigated whether PDM is expressed on fibroblasts and cancer cells in clinical tissue samples, and whether the presence of PDM-expressing colorectal cancer cells is correlated with clinicopathological features of patients.
  
  
  METHODS
  Immunohistochemistry was conducted to detect P4H9 on clinical tissue samples from 156 patients with colorectal cancer. Risk factors for metastases and survival were calculated for clinical implication of PDM-expressing spindle-shaped fibroblasts.
  
  
  RESULTS
  Multivariate analysis showed that PDM-expressing spindle-shaped fibroblasts were an independent risk factor for lymph node metastasis, hematogenous metastasis, and poor survival. A Kaplan-Meier survival curve indicated that PDM-expressing spindle-shaped fibroblasts were associated with shorter survival time (P<0.0001). Immunofluorescence showed PDM expression on CCD-18Co fibroblasts and two colorectal cancer cell lines (HCT116 and HCT-15).
  
  
  CONCLUSIONS
  PDM-expressing spindle-shaped fibroblasts are associated with metastasis and shorter survival in colorectal cancer patients. PDM-expressing spindle-shaped fibroblasts may have a role in eliciting the malignant phenotype of colorectal cancer.
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Yokoyama
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ieda
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Mitani
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Katsunari
authors.initials: K
authors.lastname: Takifuji
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hotta
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Shively
authors.affiliation: Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama 641-8510, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens / Q000737:chemistry* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D018821:CD18 Antigens; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D000939:Epitopes