4680

CEACAM6

Pancreatic cancer is a disease with an extremely poor prognosis. The acquisition of invasion properties in pancreatic cancer is accompanied by the process of epithelial-mesenchymal transition (EMT). Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is emerging as an important determinant of the malignant phenotype in a range of cancers, including pancreatic cancer. Therefore, the aim of this study was to evaluate the potential involvement of CEACAM6 in the invasion and metastasis of pancreatic cancer cells via EMT regulation. The results of our study showed a positive association between CEACAM6 expression and poor prognosis of pancreatic cancer, differentiation and lymph node metastasis. Elevated levels of CEACAM6 in pancreatic cancer cells promoted EMT, migration and invasion in vitro and metastasis in animal models, whereas shRNA-mediated CEACAM6 knockdown had the opposite effect. Furthermore, we demonstrated that miR-29a/b/c specific for CEACAM6 could regulate its expression at the post-transcriptional level. Collectively, our findings identified CEACAM6, which is regulated by miR-29a/b/c, as an important positive regulator of EMT in pancreatic cancer offering an explanation for how elevated levels of CEACAM6 are likely to contribute to the highly metastatic phenotype of pancreatic cancer.

BACKGROUND: Aim of this study was to assess the biological function in tumor progression and metastatic process carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 in pancreatic adenocarcinoma (PDAC). EXPERIMENTAL DESIGN: CEACAM knock down cells were established and assessed in vitro and in a subcutaneous and intraperitoneal mouse xenograft model. Tissue and serum expression of patients with PDAC were assessed by immunohistochemistry (IHC) and by enzyme linked immunosorbent assays. RESULTS: Presence of lymph node metastasis was correlated with CEACAM 5 and 6 expression (determined by IHC) and tumor recurrence exclusively with CEACAM 6. Patients with CEACAM 5 and 6 expression showed a significantly shortened OS in Kaplan-Meier survival analyses. Elevated CEACAM6 serum values showed a correlation with distant metastasis and. Survival analysis revealed a prolonged OS for patients with low serum CEACAM 1 values. In vitro proliferation and migration capacity was increased in CEACAM knock down PDAC cells, however, mice inoculated with CEACAM knock down cells showed a prolonged overall-survival (OS). The number of spontaneous pulmonary metastasis was increased in the CEACAM knock down group. CONCLUSION: The effects mediated by CEACAM expression in PDAC are complex, though overexpression is correlated with loco-regional aggressive tumor growth. However, loss of CEACAM can be considered as a part of epithelial-mesenchymal transition and is therefore of rather importance in the process of distant metastasis.