The expression of adhesion molecules and the influence of inflammatory cytokines on the adhesion of human pancreatic carcinoma cells to mesothelial monolayers. 2006

Wilhelmina M U van Grevenstein, and Leo J Hofland, and Johannes Jeekel, and Casper H J van Eijck
Laboratories for Experimental Surgery and Oncology, Erasmus Medical Center Rotterdam, The Netherlands.

OBJECTIVE Pancreatic cancer has a tremendously deplorable prognosis. Peritoneal dissemination frequently occurs after surgical resection of the tumor. Specific adhesion molecules may be of great importance in local tumor recurrence. These adhesion molecules may be influenced by inflammatory cytokines produced during surgery. The aim of this study was to investigate the effects of inflammatory cytokines, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), on the interaction between pancreatic tumor cells and mesothelial cells. METHODS An experimental in vitro model was designed using Panc-1, MiaPaCa-2, and BxPC-3 pancreatic carcinoma cell lines. Primary cultures of mesothelial cells were incubated with the inflammatory cytokines, and after the incubation, the adherence of the different pancreatic cell lines was measured. By means of immunocytochemical staining and enzyme immunoassay, the expression of adhesion molecules (ICAM-1, VCAM-1, and CD44) and counterparts (LFA-1 and VLA-4) was investigated. RESULTS Preincubation of the mesothelial monolayer with IL-1beta or TNF-alpha resulted in enhanced tumor cell adhesion of the MiaPaCa-2 and BxPC-3 cells. The amount of stimulation for the MiaPaCa-2 cells was more than 100% versus the control situation and for BxPC-3 cells between 20% to 35%. IL-6 did not affect the tumor cell adhesion of the MiaPaCa-2 and BxPC-3 cells. The adherence of Panc-1 was not enhanced after preincubation of the mesothelial monolayers with the inflammatory cytokines. Mesothelial cells show a significant enhancement of expression of ICAM-1, VCAM-1, and CD44 after stimulation with IL-1beta and TNF-alpha. CONCLUSIONS The presented results prove that IL-1beta and TNF-alpha are significant stimulating factors in pancreatic tumor cell adhesion in vitro and may therefore account for tumor recurrence to the peritoneum in vivo. The immunocytochemical staining results demonstrate that ICAM-1 and CD44 important adhesion molecules and interference with their function may decrease the incidence of peritoneal tumor recurrence after curative resection of pancreatic cancer.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D010190 Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA). Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015815 Cell Adhesion Molecules Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. Cell Adhesion Molecule,Intercellular Adhesion Molecule,Intercellular Adhesion Molecules,Leukocyte Adhesion Molecule,Leukocyte Adhesion Molecules,Saccharide-Mediated Cell Adhesion Molecules,Saccharide Mediated Cell Adhesion Molecules,Adhesion Molecule, Cell,Adhesion Molecule, Intercellular,Adhesion Molecule, Leukocyte,Adhesion Molecules, Cell,Adhesion Molecules, Intercellular,Adhesion Molecules, Leukocyte,Molecule, Cell Adhesion,Molecule, Intercellular Adhesion,Molecule, Leukocyte Adhesion,Molecules, Cell Adhesion,Molecules, Intercellular Adhesion,Molecules, Leukocyte Adhesion
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D018799 Intercellular Adhesion Molecule-1 A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. Antigens, CD54,CD54 Antigens,ICAM-1,CD54 Antigen,Antigen, CD54,Intercellular Adhesion Molecule 1
D018960 Hyaluronan Receptors Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary THYMOCYTES; GRANULOCYTES; MACROPHAGES; erythrocytes, and fibroblasts. Their interaction with HYALURONIC ACID mediates binding of lymphocytes to high endothelial VENULES. Antigens, CD44,CD44 Antigens,Hyaluronan-Binding Protein,Receptors, Hyaluronan,CD44 Antigen,Chondroitin Sulfate Proteoglycan 8,Hyaluronan Receptor,Hyaluronic Acid Binding Protein,Antigen, CD44,Hyaluronan Binding Protein,Receptor, Hyaluronan

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