Expression and function of VLA-alpha 2, -alpha 3, -alpha 5 and -alpha 6-integrin receptors in pancreatic carcinoma.
The expression of the VLA-integrins alpha 2, alpha 3, alpha 5 and alpha 6 was studied immunohistochemically in tissue samples from ductal pancreatic cancer, chronic pancreatitis, normal pancreas and in 8 cell lines of ductal human pancreatic cancer. Furthermore, adhesion assays on purified extracellular matrix (ECM)-compounds were used to define the function of alpha 2, alpha 3, alpha 5 and alpha 6 in pancreatic cancer cells. Immunohistochemically, VLA alpha 2 and VLA alpha 6 were moderately to strongly expressed on the basal surface of ductal and acinar cells in normal pancreatic tissue, while centro-acinar cells predominantly expressed VLA alpha 3 and VLA alpha 5. Pancreatic carcinoma showed intense staining for VLA alpha 2 and VLA alpha 6 with a diffuse distribution on the cell surface. The redistribution of VLA alpha 2 and VLA alpha 6 may reflect a loss of spatial arrangement of tumor cells and their ability to interact randomly with extracellular matrix structures during invasion and metastasis. Expression of VLA alpha 3 and VLA alpha 5 in pancreatic carcinoma was heterogeneous, ranging from moderate to weak, and was lost in about 50% of the cells. Two pancreatic carcinoma cell lines (PC 3, PC 44) were further investigated in adhesion assays. Monoclonal antibodies (MAbs) against alpha 2 (GI 9, 10-G-11) were able to inhibit tumor-cell adhesion to collagen IV (59%-72%) in both cell lines. A MAb against alpha 6 (GoH3) inhibited tumor-cell adhesion to laminin (52%-86%) in both cell lines. These results suggest that alpha 2 is a collagen-binding site and alpha 6 a laminin-binding site in pancreatic cancer cells. The anti-alpha 5-MAb SAM I inhibited adhesion of PC3 to fibronectin (76%), being without effect in PC44. Adhesion of both cell lines to fibronectin was almost completely inhibited by RGDS (85%-88%). Thus, alpha 5 is a functionally important fibronectin binding site in some pancreatic carcinoma cells, suggesting further RGD-dependent fibronectin binding sites in other pancreatic carcinoma cells.
Weinel
R J
RJ
Department of Surgery and Pathology, Philipps University, Marburg, Germany.
Rosendahl
A
A
Neumann
K
K
Chaloupka
B
B
Erb
D
D
Rothmund
M
M
Santoso
S
S
D000595:Amino Acid Sequence; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D009842:Oligopeptides; D016029:Receptors, Very Late Antigen