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.

Hollow spheroids beyond the invasive margin indicate the malignant potential of colorectal cancer

“…Stable CEACAM1-4S transfected LS174T cells had significantly reduced CEACAM1-4L mRNA and protein levels, which was confirmed by RT-PCR and western blot analyses as previously described 25. The CEACAM1 and CEACAM1-4L protein levels of these cells were significantly suppressed compared to those of the parental or vector-transfected cells (control) 25. CEACAM1-4S overexpressing cells reduced the number of colorectal hollow spheroids formed (p<0.01) (figure 3D).…”

“…In colorectal cancer, it is known that down-regulation of CEACAM1 occurs at the adenoma or early cancer stage,14 15 and CEACAM1 is re-expressed in advanced colorectal cancers 23 24. Recently, we showed that re-expressed CEACAM1, especially with long cytoplasmic domain dominance, in advanced colorectal carcinoma is associated with tumour metastasis and shorter survival 25. In the present study, we demonstrate that CEACAM1 isoform balance with long cytoplasmic domain dominance plays an important role in hollow spheroid formation in colorectal cancer.…”

Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma

“…The authors concluded that CEACAM1 actively contributed to tumor progression [25]. The reason for this discrepancy warrants further investigation but could be that CEACAM1 may have different roles in different cancers as discussed above [26, 27]. …”

Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases

“…The CEACAM1 reactivity might be associated with metastatic spread, e.g., down-regulated in the early stage of the cancer and re-expressed in metastatic colon cancer [36]. The density of CEACAM1 expression was stronger at the invasion front of colorectal cancer in patients [37]. CEACAM1-L dominance might be an independent risk factor for lymph node metastasis, hematogenous metastasis, or short survival, and an important limiting factor for the invasion and migration of cancer cells.…”