Dataset Information

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

ABSTRACT:

Background

CD166, 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.

Methods

We 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.

Results

Immunohistochemistry 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.

Conclusions

CD166+ 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.

SUBMITTER: Fujiwara K

PROVIDER: S-EPMC4164537 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

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

Fujiwara Kenji K Ohuchida Kenoki K Sada Masafumi M Horioka Kohei K Ulrich Charles D CD Shindo Koji K Ohtsuka Takao T Takahata Shunichi S Mizumoto Kazuhiro K Oda Yoshinao Y Tanaka Masao M

PloS one 20140915 9

<h4>Background</h4>CD166, 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.<h4>Methods</h4>We performed immunohistochemistry and flow cytometry to analyze the expression of CD166 in surgical pancreatic tissues and pancreati ...[more]

PMID: 25221999

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Project description:Activated leukocyte cell adhesion molecule (ALCAM, or CD166) is a cell adhesion molecule and one of potential tumour metastasis 'soil' receptors that via homotypic and heterotypic interactions, mediates cancer cell adhesion. The present study investigated clinical, pathological and prognostic values of ALCAM in patients with pancreatic cancer. Human pancreatic cancer (PANC-1 and Mia PaCa-2) and human vascular endothelial cell lines were used to construct cell models differentially expressing levels of ALCAM. Tumour-endothelial interaction and tumour migration were assessed by a DiI-based method and electric cell-substrate impedance sensing (ECIS) assay. Pancreatic cancer tissues (n=223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts, which were also analysed against clinical, pathological and clinical outcomes of the patients. ALCAM protein was assessed by immunohistochemistry on a tissue array. Our study demonstrate that pancreatic cancer tissues had significantly higher levels of ALCAM transcripts than normal tissues (P<0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P=0.018), and this finding was further supported by ROC analysis (P=0.016). Multivariant analysis showed that ALCAM is an independent prognosis factor for overall survival (HR=5.485), with both nodal status and TNM staging contributing to the model (HR=2.578 and 3.02, respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P=0.021, with vs without tumour embolism). Levels of ALCAM were found to be a determinant factor to adherence of the pancreatic cancer cells to vascular endothelial cells, as demonstrated by pancreatic cancer cell models genetically engineered to express differential levels of ALCAM. The tumour-endothelial interaction mediated by ALCAM was readily blocked by addition of soluble ALCAM. Our data supports the conclusion that ALCAM expression is aberrant in pancreatic cancer and its raised expression is an independent prognostic factor for the survival of the patients and the microvascular embolism by cancer cells. Our results suggest that ALCAM plays a key role in mediating tumour-endothelial cell interactions and enhancing tumour embolism in pancreatic cancer, and targeting ALCAM represents a potential therapeutic strategy for treating human pancreatic cancer.

Project description:In epithelial-derived cancers, altered regulation of cell-cell adhesion facilitates the disruption of tissue cohesion that is central to the progression to malignant disease. Although numerous intercellular adhesion molecules participate in epithelial adhesion, the immunoglobulin superfamily (IgSF) member activated leukocyte cell adhesion molecule (ALCAM), has emerged from multiple independent studies as a central contributor to tumor progression. ALCAM is an archetypal member of the IgSF with conventional organization of five Ig-like domains involved in homo- and heterotypic adhesions. Like many IgSF members, ALCAM is broadly expressed and involved in cellular adhesion across many cellular processes. While the redundancy of intercellular adhesion molecules (CAMs) could diminish the impact of any single CAM, consistent correlation between ALCAM expression and patient outcome for multiple cancers underscores its role in tumor progression. Unlike most oncogenes and tumor suppressors, ALCAM is neither mutated nor amplified or deleted. Experimental disruption of ALCAM-mediated adhesions implies that this IgSF member contributes to tumor progression through dynamic turnover of the protein at the cell surface. Since ALCAM is not frequently altered at the gene level, it appears to promote malignant behavior through regulation of its availability rather than its specific activity. These observations help explain its heterogeneous expression within malignant disease and the drastic changes in protein levels across tumor progression. To reveal how ALCAM contributes to tumor progression, we review regulation of its gene expression, alternative splicing, targeted proteolysis, binding partners, and surface shedding within the context of cancer. Studying ALCAM regulation has led to a novel understanding of the fine-tuning of cell adhesive state through the utilization of otherwise normal regulatory processes, which thereby enable tumor cell invasion and metastasis.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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