Ability of kallikrein to generate angiotensin II-like pressor substance and a proposed ‘kinin–tensin enzyme system’

Arakawa, Kikuo; Maruta, H

doi:10.1038/288705a0

Cited by 63 publications

(33 citation statements)

References 12 publications

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“…The mechanism might involve activation by trypsin of an enzyme capable of so doing, such as tonin. 12 Conversely, activation of renin-known to be relatively abundant in the uterine wall 13 ' 14 and to increase considerably during pregnancy 14 -could be the first step of another such mechanism. This would require the Ang I generated to be converted to Ang II, a process heretofore considered unlikely, given the low Ang I converting enzyme activity ascribed to the rat uterus.…”

Section: Discussionmentioning

confidence: 99%

Oxytocic effect of trypsin on the isolated rat uterus.

1994

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To study the oxytocic effect of trypsin, we measured the force of isometric contraction in uteri isolated from estrogenized rats exposed to trypsin (8. ]-bradykinin). We found that saralasin or DuP 753, but not the kinin antagonist, displaced the dose-response curve to the right. Exposure to exogenous angiotensin I desensitized the preparation to further doses of either angiotensin I or II or trypsin, without altering the effects of oxytocin or bradykinin. Enalaprilat (an angiotensin I converting enzyme inhibitor) or pepstatin A (a renin inhibitor) also displaced the dose-response curve to trypsin to the right, without altering the effects of oxytocin or angiotensin II. Our results indicate that the response to trypsin is mediated by an agent produced from a substrate present in the uterus and acting on the angiotensin II type 1 receptor and are consistent with both renin and angiotensin I converting enzyme being involved in its mechanism of action, thus supporting the notions that the reninangiotensin system may be important in the late stages of pregnancy and that serine proteases existing in the uterus may contribute to its activation.

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Section: Discussionmentioning

confidence: 99%

Oxytocic effect of trypsin on the isolated rat uterus.

1994

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“…Meanwhile, Arakawa et al (7) demonstrated that trypsin generated angiotensin II (AngII) from human plasma protein in the absence of angiotensin converting enzyme (ACE) at weakly acidic pH 7.0). Our previous report showed that pancreatic cancer tissues had higher trypsinogen expression and higher AngII concentrations than other solid tumors, such as HCC and colorectal cancer (8).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

et al. 2010

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Abstract. Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of ·-smooth muscle actin (·-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis.

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“…Gastric cancer cells express trypsinogen that converts to trypsin at pH 5.5 [25]. Furthermore, mast cells that migrate into gastric cancer tissues express tryptase.…”

Section: -1 the Mechanism Of Secretion Of Tgf-β By Gastric Cancer Cellsmentioning

confidence: 99%

The Importance of Controlling the TGF-β Signaling Pathway in the Gastric Cancer Microenvironment

Koyama¹,

Fushida²,

Ohta³

2017

Preprint

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Gastric cancer is an intractable disease with a high incidence of peritoneal dissemination and obstructive symptoms (e.g. ileus, jaundice, and hydronephrosis) arising from accompanying marked fibrosis. Microenvironmental interactions between cancer cells and stromal cells are the suggested cause of the disease. Transforming growth factor (TGF-β) is an intriguing cytokine exhibiting dual roles in malignant disease, acting as an important mediator of cancer invasion, metastasis, and angiogenesis as well as exhibiting antitumor functions. Moreover, the TGF-β pathway contributes to the generation of a favorable microenvironment for tumor growth and metastasis throughout the steps of carcinogenesis. Among these effects, TGF-β induces the epithelial-to-mesenchymal transition with prometastatic functions, contributes to the conversion of stromal cells to carcinoma-associated fibroblasts, and suppresses the function of immune cells, which compromises the antitumor immune response, leading to cancer progression and stromal fibrosis. In this review, we address the role of the essential TGF-β signaling pathway in the regulation of the activities of components of the tumor microenvironment of gastric cancer and how this contributes to tumor progression and stromal fibrosis. We then explore the potential to optimize therapy that inhibits TGF-β signaling in the preclinical and clinical settings of gastric cancer.

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Ability of kallikrein to generate angiotensin II-like pressor substance and a proposed ‘kinin–tensin enzyme system’

Cited by 63 publications

References 12 publications

Oxytocic effect of trypsin on the isolated rat uterus.

Oxytocic effect of trypsin on the isolated rat uterus.

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

The Importance of Controlling the TGF-β Signaling Pathway in the Gastric Cancer Microenvironment

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Ability of kallikrein to generate angiotensin II-like pressor substance and a proposed ‘kinin–tensin enzyme system’

Cited by 63 publications

References 12 publications

Oxytocic effect of trypsin on the isolated rat uterus.

Oxytocic effect of trypsin on the isolated rat uterus.

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

The Importance of Controlling the TGF-&beta; Signaling Pathway in the Gastric Cancer Microenvironment

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The Importance of Controlling the TGF-β Signaling Pathway in the Gastric Cancer Microenvironment