Background: Epithelial to mesenchymal transitions (EMT) are vital for tumor progression and metastasis. Several inducers of EMT are transcription factors that repress E-Cadherin expression such as Snail, Slug and Twist. In this study we aimed to examine the expression and role of these transcription factors in pancreatic cancer.
Methods: The expression of Snail, Slug, Twist, and E-Cadherin was detected by immunohistochemistry in tissue samples from 36 patients with pancreatic ductal adenocarcinoma. Four human pancreatic cancer cell lines (Capan-1, HPAF-2, MIAPaCa-2, and Panc-1) and human endothelial cells (HUVEC; control) were analyzed by RT-PCR, real-time PCR and western blotting. An orthotopic nude mouse model was applied for in vivo experiments: tumors were derived from the four human pancreatic cancer cell lines and animals (12 per group) observed for 14 weeks. Expression of the transcription factors and E-Cadherin was correlated with tumor spread and metastasis (dissemination score) in the mice.
Results: 78% of human pancreatic cancer tissues showed an expression of Snail, and 50% of the patients displayed positive expression of Slug. Twist showed no or only weak expression. A strong Snail expression in undifferentiated cancer cell lines (MIAPaCa-2 and Panc-1) was associated with low E-Cadherin and extensive metastasis in the mouse model. In contrast, low Snail and strong E-Cadherin expression in more differentiated cells lines (Capan-1, HPAF-2) corresponded with a significantly reduced tumor spread in the animals (table). Snail mRNA expression correlated positively with metastatic potential of the cancer cells (r = 0.8), whereas a negative correlation was found between E-Cadherin and metastasis (r = -0.9).
Conclusions: The transcription factors and EMT-regulators Snail and Slug are expressed in pancreatic cancer but not in normal tissue. The upregulation of Snail is associated with low expression of the adhesion molecule E-Cadherin, suggesting a role for Snail in the progression and metastasis of human pancreatic carcinomas.

	Relative mRNA concentration
Cell line	Snail	E-Cadherin	Metastasis (Dissemination Score)
Capan-1	0.39	7.64	5.9 ± 0.6*
HPAF-2	1.03	5.58	6.9 ± 0.5*
MIAPaCa-2	7.17	0.10	14.3 ± 0.9
Panc-1	11.42	0.69	10.8 ± 0.7
HUVEC (Control)	1	1

p<0.05: * vs. MIAPaCa-2 / Panc-1