Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: Angiogenesis in chronic pancreatitis and in pancreatic cancer
R. Kuehn et al., Angiogenesis, angiogenic growth factors, and cell adhesion molecules are upregulated in chronic pancreatic diseases: Angiogenesis in chronic pancreatitis and in pancreatic cancer, PANCREAS, 18(1), 1999, pp. 96-103
Recent epidemiologic evidence suggests that patients with chronic pancreati
tis (CP) have an increased risk of developing pancreatic carcinoma (PCA). I
n spite of numerous similarities in both diseases, mechanisms for progressi
on from CP to PCA are poorly understood. We hypothesized that enhanced angi
ogenesis might play a pivotal role in the etiology and histopathology of bo
th CP and PCA, and thus form a possible link between precancer and carcinom
a. In surgical specimens of 18 patients with CP, 10 with PCA, and 18 contro
ls, absolute numbers of blood vessels and relative blood vessel density wer
e assessed after immunostaining of endothelial cells for von Willebrand fac
tor and PECAM-1 (platelet/endothelial cell adhesion molecule-1). Furthermor
e, the expression of cell adhesion molecules ICAM-1 (intercellular adhesion
molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) and of VEGF (va
scular endothelial growth factor) was investigated in all specimens. Both C
P 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 mm(2),
and in CP, 99.2 +/- 7.4 per mm(2). The mean vessel count in controls was 2
5.1 +/- 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 ve
ssel 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 e
xpressed only at low levels in endothelial cells. VCAM-1 was strongly expre
ssed in acinar cells as well as in ductal cells. In CP and PCA, VEGF was st
rongly expressed in ductal cells in CP as well as in cancer cells. We shaw
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 ta
rget for prevention or therapy in chronic pancreatic diseases.