Angiotensin converting enzyme-independent, local angiotensin II-generation in human pancreatic ductal cancer tissues.
Hypovascularity is an outstanding characteristic of pancreatic ductal cancer by diagnostic imaging: most pancreatic ductal cancers are hypovascular or avascular, and tumor vessels are seldom seen on angiography. However, we found that the vasculature was not always poor on angiography of surgically resected specimens of locally advanced pancreatic ductal cancers. To elucidate these controversial findings, we focused on angiotensin II, a vasoconstrictor which is directly produced from angiotensinogen at acidic pH by active trypsin. We examined whether a local angiotensin II-generating system exists in pancreatic ductal cancer tissue. We measured angiotensin II concentration and angiotensin converting enzyme (ACE) activity in tissues from normal pancreas, pancreatic ductal cancers, colon cancers, and hepatocellular carcinomas. After surgically resected specimens were homogenized, angiotensin II concentration and ACE activity in tissues were measured using the florisil method and the Kasahara method, respectively. Tissue angiotensin II levels in pancreatic ductal cancer (n=13) were significantly higher than those of normal pancreas (n=7), colon cancers (n=7), or hepatocellular carcinomas (n=7). However, there was no significant difference in the ACE activity in tissue between them. This study provides in vivo evidence of an ACE-independent, angiotensin II-generating system in pancreatic ductal cancer tissues and suggests that locally formed angiotensin II may act on the pre-existing pancreatic arteries around the tumor, leading to formation of hypovascular or avascular regions.
Ohta
Tetsuo
T
Department of Gastroenterologic Surgery, Kanazawa University Hospital, Takara-machi 13-1, Kanazawa 920-0934, Japan. ohtat@surg2.m.kanazawa-u.ac.jp
Amaya
Kohji
K
Yi
Shuangqin
S
Kitagawa
Hirohisa
H
Kayahara
Masato
M
Ninomiya
Itasu
I
Fushida
Sachio
S
Fujimura
Takashi
T
Nishimura
Gen-Ichi
G
Shimizu
Koichi
K
Miwa
Koichi
K
D000804:Angiotensin II / Q000096:biosynthesis* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D053818:Chymases; D003110:Colonic Neoplasms / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases; D014357:Trypsin