CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells.

Kenji Fujiwara,Kazuhiro Mizumoto,Shunichi Takahata,Masao Tanaka,Charles D Ulrich,Koji Shindo,Kohei Horioka,Masafumi Sada,Takao Ohtsuka,Yoshinao Oda,Kenoki Ohuchida,Dhyan Chandra

doi:10.1371/journal.pone.0107247

Abstract

BackgroundCD166, also known as activated leukocyte cell adhesion molecule (ALCAM), is expressed by various cells in several tissues including cancer. However, the role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer.MethodsWe performed immunohistochemistry and flow cytometry to analyze the expression of CD166 in surgical pancreatic tissues and pancreatic cancer cell lines. The differences between isolated CD166+ and CD166- pancreatic cancer cells were analyzed by invasion and migration assays, and in mouse xenograft models. We also performed quantitative RT-PCR and microarray analyses to evaluate the expression levels of CD166 and related genes in cultured cells.ResultsImmunohistochemistry revealed high expression of CD166 in pancreatic cancer tissues (12.2%; 12/98) compared with that in normal pancreas controls (0%; 0/17) (p = 0.0435). Flow cytometry indicated that CD166 was expressed in 33.8–70.2% of cells in surgical pancreatic tissues and 0–99.5% of pancreatic cancer cell lines. Invasion and migration assays demonstrated that CD166- pancreatic cancer cells showed stronger invasive and migratory activities than those of CD166+ cancer cells (p<0.05). On the other hand, CD166+ Panc-1 cells showed a significantly stronger colony formation activity than that of CD166- Panc-1 cells (p<0.05). In vivo analysis revealed that CD166+ cells elicited significantly greater tumor growth than that of CD166- cells (p<0.05) in both subcutaneous and orthotopic mouse tumor models. mRNA expression of the epithelial-mesenchymal transition activator Zeb1 was over-expressed in CD166- cells (p<0.001). Microarray analysis showed that TSPAN8 and BST2 were over-expressed in CD166+ cells, while BMP7 and Col6A1 were over-expressed in CD166- cells.ConclusionsCD166+ pancreatic cancer cells are strongly tumorigenic, while CD166- pancreatic cancer cells exhibit comparatively stronger invasive and migratory activities. These findings suggest that CD166 expression is related to different functions in pancreatic cancer cells.

Highlights

Pancreatic cancer is one of the most lethal human malignancies, with a 5-year survival rate of less than 5% [1]
These findings suggest that CD166 expression is related to different functions in pancreatic cancer cells
We found that CD166 expression was associated with perineural invasion (p = 0.037, Table S1), but not prognosis using Kaplan–Meier survival analysis (p = 0.1473, Figure 1B)

Summary

Introduction

Pancreatic cancer is one of the most lethal human malignancies, with a 5-year survival rate of less than 5% [1]. This poor outcome is largely because early diagnosis is uncommon and conventional therapeutics such as surgical resection, chemotherapy, and radiotherapy have limited efficacy [1,2]. CSCs comprise a very small population of cancer cells that have the ability to initiate and sustain tumor formation [3]. The role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer

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Conclusion