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Cysteine cathepsins: multifunctional enzymes in cancer
TLDR
Direct proof for causal roles in tumour growth, migration, invasion, angiogenesis and metastasis has been shown by downregulating or ablating the expression of individual cysteine cathepsins in tumours and in transgenic mouse models of human cancer.
Acidity generated by the tumor microenvironment drives local invasion.
TLDR
Oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis.
Pericellular pH affects distribution and secretion of cathepsin B in malignant cells.
TLDR
It is suggested that the redistribution of active cathepsin B to the surface of malignant cells and its secretion may facilitate invasion of these cells.
Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues.
TLDR
The results suggest that cathepsin B at or near the surface of malignant tumour cells may play a functional role in the focal dissolution of extracellular matrices.
Unraveling the role of proteases in cancer.
Bicarbonate increases tumor pH and inhibits spontaneous metastases.
TLDR
Oral NaHCO(3) selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer, suggesting that inhibition of this tumor acidity will reduce the incidence of in vivo metastases.
Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice.
TLDR
The current experimental study shows that cathepsin B is up-regulated in a mouse model of adenomatous polyposis and this detection technology can be adapted to endoscopy or tomographic optical imaging methods for screening of suspicious lesions and potentially for molecular profiling in vivo.
Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments.
TLDR
Assessment of the effect of low pH on human breast carcinoma cells and mouse tumors argues that acidic conditions in the tumor microenvironment promote autophagy, and that chronicAutophagy occurs as a survival adaptation in this setting.
Cysteine cathepsins in human cancer
TLDR
Clinically, the levels, activities and localization of cysteine cathepsins and their endogenous inhibitors have been shown to be of diagnostic and prognostic value and could lead to the development of more efficacious therapies.
Cathepsin B expression and localization in glioma progression and invasion.
TLDR
The hypothesis that cathepsin B plays a role in human glioma progression and invasion is supported by substantial evidence and data support the hypothesis.
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