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.

Protease-activated receptor-2 expression and the role of trypsin in cell proliferation in human pancreatic cancers.

Protease-activated receptor (PAR)-2 is a G protein-coupled receptor that is activated by trypsin. The purpose of this study was to examine PAR-2 expression and the role of trypsin in cell proliferation in human pancreatic cancer cells. All four pancreatic cancer cell lines studied, from well to undifferentiated types, AsPC-1, BxPC-3, Panc-1, and MIAPaCa-2, had significant levels of PAR-2 mRNA detected by reverse transcription-polymerase chain reaction, and showed a band of about 55 kDa corresponding to the known molecular weight of PAR-2: AsPC-1, BxPC-3 and Panc-1 showed a strong band, and MIAPaCa-2 showed a weak one.

[Intrinsic angiotensin II-generating system in human pancreatic cancer tissues].

To clarify whether an intrinsic angiotensin II-generating system exists in human advanced pancreatic cancer tissues, we measured angiotensin II concentration and angiotensin converting enzyme (ACE) activity in tissues of normal pancreas, pancreatic cancers, colon cancers and hepatocellular carcinomas. After the surgically resected specimens were homogenized, angiotensin II concentration and ACE activity in tissues were measured using the florisil method and Kasahara's method, respectively. Tissue angiotensin II levels in pancreatic cancers (n = 13) were significantly higher than those of normal pancreas (n = 7), colon cancers (n = 7), or hepatocellular carcinomas (n = 7).