Activated leukocyte cell adhesion molecule regulates the interaction between pancreatic cancer cells and stellate cells

• Published in: Molecular medicine reports Vol. 14; no. 4; pp. 3627 - 3633
• Main Authors: Zhang, Wei-Wei, Zhan, Shu-Hui, Geng, Chang-Xin, Sun, Xin, Erkan, Mert, Kleeff, Jörg, Xie, Xiang-Jun
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: activated leukocyte cell adhesion molecule; Activated-Leukocyte Cell Adhesion Molecule - analysis; Activated-Leukocyte Cell Adhesion Molecule - genetics; Adenocarcinoma; Apoptosis; Autophagy; Biotechnology; Breast cancer; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - pathology; Care and treatment; CD166; Cell adhesion & migration; Cell adhesion molecules; Cell Communication; Cell culture; Cell Line; Colon; Development and progression; Enzyme-linked immunosorbent assay; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Glycoproteins; Health aspects; Humans; Hypoxia; Immunoblotting; Immunocytochemistry; Immunoglobulins; Immunohistochemistry; Invasiveness; Localization; Metastases; Metastasis; microenvironment; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Pancreas - cytology; Pancreas - metabolism; Pancreas - pathology; Pancreatic cancer; pancreatic cancer cells; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; pancreatic stellate cells; Pancreatic Stellate Cells - cytology; Pancreatic Stellate Cells - metabolism; Pancreatic Stellate Cells - pathology; Pancreatitis; Pancreatitis - genetics; Pancreatitis - pathology; Penicillin; Polymerase chain reaction; Prostate; Reverse transcription; RNA, Messenger - genetics; RNA, Small Interfering - genetics; siRNA; Stellate cells; Transforming growth factor; Transforming growth factor-b; Tumor necrosis factor; Tumorigenesis; Tumors; Up-Regulation; Germany
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.5681

Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a transmembrane glycoprotein that is involved in tumor progression and metastasis. In the present study, the expression and functional role of ALCAM in pancreatic cancer cells and pancreatic stellate cells (PSCs) was investigated. Tissue specimens were obtained from patients with pancreatic ductal adenocarcinoma (n=56) or chronic pancreatitis (CP; n=10), who underwent pancreatic resection, and from normal pancreatic tissue samples (n=10). Immunohistochemistry was used to analyze the localization and expression of ALCAM in pancreatic tissues. Subsequently, reverse transcription-quantitative polymerase chain reaction and immunoblotting were applied to assess the expression of ALCAM in pancreatic cancer Panc-1 and T3M4 cells, as well as in PSCs. An enzyme-linked immunosorbent assay was used to measure ALCAM levels in cell culture medium stimulated by hypoxia, tumor necrosis factor (TNF)-α and transforming growth factor-β. Silencing of ALCAM was performed using ALCAM small interfering (si)RNA and immunocytochemistry was used to analyze the inhibition efficiency. An invasion assay and a cell interaction assay were performed to assess the invasive ability and co-cultured adhesive potential of Panc-1 and T3M4 cells, as well as PSCs. Histologically, ALCAM expression was generally weak or absent in pancreatic cancer cells, but was markedly upregulated in PSCs in pancreatic cancer tissues. ALCAM was highly expressed in PSCs from CP tissues and PSCs surrounding pancreatic intraepithelial neoplasias, as well as in pancreatic cancer cells. ALCAM mRNA was highly expressed in PSCs, with a low to moderate expression in T3M4 and Panc-1 cells. Similar to the mRNA expression, immunoblotting demonstrated that ALCAM protein levels were high in PSCs and T3M4 cells, but low in Panc-1 cells. The expression of TNF-α increased, while hypoxia decreased the secretion of ALCAM in pancreatic cancer Panc-1 and T3M4 cells, and also in PSCs. Silencing of ALCAM by siRNA revealed no significant alteration in the invasion of pancreatic cancer cells, however, it inhibited the invasive ability of PSCs, and decreased the interaction between Panc-1 cells and PSCs. In conclusion, ALCAM is upregulated in PSCs of pancreatic cancer tissues, suggesting a potential role of ALCAM in regulating pancreatic cancer cell-PSC interactions.