title: Re-expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer.
abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is known to be downregulated at the transcriptional level in adenoma and carcinoma. Recent reports have shown that CEACAM1 is overexpressed at protein level in colorectal cancer and correlated with clinical stage. The reason why colorectal cancer cells re-expressed CEACAM1 remains unclear. The aim of our study was to clarify the implication of CEACAM1 re-expression in colorectal cancer. Immunohistochemical analyses were conducted with CEACAM1 long (CEACAM1-L) or short (CEACAM1-S) cytoplasmic domain-specific antibodies on clinical samples from 164 patients with colorectal cancer. The risk factors for metastasis and survival were calculated for clinical implication of CEACAM1 re-expression. Invasion chamber and wound healing assays were performed for the effect of CEACAM1 expression on invasion and migration of colorectal cancer cells. CEACAM1-L and CEACAM1-S stained with greater intensity at the invasion front than at the luminal surface of tumors. Differences between the long and short cytoplasmic isoform expression levels were observed at the invasion front. Multivariate analysis showed that CEACAM1-L dominance was an independent risk factor for lymph node metastasis, hematogenous metastasis and short survival. The Kaplan-Meier evaluation demonstrated that CEACAM1-L dominance was associated with shorter survival time (p < 0.0001). In the invasion chamber and wound healing assays, CEACAM1-L promoted invasion and migration. Re-expression of CEACAM1 is observed at the invasion front of colorectal cancer. CEACAM1-L dominance is associated with metastasis and shorter survival of the patients with colorectal cancer. CEACAM1-L dominance is important for colorectal cancer cells invasion and migration.
authors.affiliation: Second Department of Surgery, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ieda
authors.forename: Shozo
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Tamura
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: Yoshimasa
authors.initials: Y
authors.lastname: Oku
authors.forename: Toru
authors.initials: T
authors.lastname: Nasu
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Kiriyama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakamura
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 / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014162:Transfection
chemical_list: D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D020033:Protein Isoforms