title: Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: angiogenesis in chronic pancreatitis and in pancreatic cancer.
abstract: Recent epidemiologic evidence suggests that patients with chronic pancreatitis (CP) have an increased risk of developing pancreatic carcinoma (PCA). In spite of numerous similarities in both diseases, mechanisms for progression from CP to PCA are poorly understood. We hypothesized that enhanced angiogenesis might play a pivotal role in the etiology and histopathology of both CP and PCA, and thus form a possible link between precancer and carcinoma. In surgical specimens of 18 patients with CP, 10 with PCA, and 18 controls, absolute numbers of blood vessels and relative blood vessel density were assessed after immunostaining of endothelial cells for von Willebrand factor and PECAM-1 (platelet/ endothelial cell adhesion molecule-1). Furthermore, the expression of cell adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and of VEGF (vascular endothelial growth factor) was investigated in all specimens. Both CP and PCA exhibited areas of high vascular density ("hot spots"). The mean number of blood vessels in these areas in PCA was 132.2+/-16.8 per mm2, and in CP, 99.2+/-7.4 per mm2. The mean vessel count in controls was 25.1+/-5.1. Relative vessel density was increased in both PCA (41.3+/-3.5%) and CP (30.6+/-2.6%) versus controls (8.0+/-0.8%). Both absolute vessel count and relative vessel density were significantly higher (p<0.05) in PCA than in CP. Enhanced expression of ICAM-1 in CP and PCA was seen in ductal cells in CP and cancer cells. In controls, ICAM-1 and VCAM-1 were expressed only at low levels in endothelial cells. VCAM-1 was strongly expressed in acinar cells as well as in ductal cells. In CP and PCA, VEGF was strongly expressed in ductal cells in CP as well as in cancer cells. We show for the first time that angiogenic activity is increased in both CP and PCA. Based on this study, we suggest that antiangiogenesis might be a novel target for prevention or therapy in chronic pancreatic diseases.
authors.affiliation: Department of Surgery, University Hospital Eppendorf, University of Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kuehn
authors.forename: P I
authors.initials: PI
authors.lastname: Lelkes
authors.forename: C
authors.initials: C
authors.lastname: Bloechle
authors.forename: A
authors.initials: A
authors.lastname: Niendorf
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics; D002908:Chronic Disease; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008207:Lymphatic Metastasis; D008222:Lymphokines / Q000032:analysis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D015815:Cell Adhesion Molecules; D016228:Endothelial Growth Factors; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor