Plasma membrane association of cathepsin B in human prostate cancer: biochemical and immunogold electron microscopic analysis.

Background: Cathepsin B (CB), a cysteine protease, is usually found in perinuclear lysosomes of epithelial cells of normal organs and non-malignant tumors, but is associated with the plasma membranes of many solid organ malignant tumors. Plasma membrane localized CB facilitates degradation of extracellular matrix proteins and progression of tumor cells from one biological compartment to another. The activities of CB and its subcellular distribution have not been investigated in malignant prostate.

Pericellular pH affects distribution and secretion of cathepsin B in malignant cells.

Redistribution of lysosomes to the cell surface and secretion of lysosomal proteases appear to be general phenomena in cells that participate in local proteolysis. In the present study, we have determined whether malignant progression affects the intracellular distribution and secretion of the lysosomal protease cathepsin B in three model systems, each of which consists of cell pairs that differ in their degree of malignancy. The intracellular distribution of vesicles staining for cathepsin B was evaluated by immunofluorescent microscopy and the secretion of cathepsin B was evaluated by two complementary techniques: stopped assays of activity secreted into culture media; and continuous assays of activity secreted from viable (> or = 95%) cells growing on coverslips.

Increased gelatinase A (MMP-2) and cathepsin B activity in invasive tumor regions of human colon cancer samples.

Gelatinase A (MMP-2) and cathepsin B are proteinases which have been proposed to participate in human tumor invasion and metastasis. Precise quantitation of the activity of these enzymes in invading tumors has not been previously described. We utilized a novel tissue microdissection technique to determine levels of enzyme activity in specific microscopic areas of invasive human colon cancer.

Cathepsin B expression and localization in glioma progression and invasion.

The poor prognosis of human malignant gliomas is due to their invasion and recurrence, the molecular mechanisms of which remain poorly characterized. We have accumulated substantial evidence implicating the cysteine protease cathepsin B in human glioma malignancy. Increases in cathepsin B expression were observed throughout progression.

A lipoxygenase metabolite, 12-(S)-HETE, stimulates protein kinase C-mediated release of cathepsin B from malignant cells.

The process of tumor cell invasion of the basement membrane is proposed to consist of three steps: attachment, local proteolysis and migration. 12-(S)-HETE, a 12-lipoxygenase metabolite of arachidonic acid, upregulates surface expression of integrin cytoadhesins and an autocrine motility factor receptor, suggesting that this metabolite may play an important regulatory function in tumor cell invasion. In the present study, we determined whether 12-(S)-HETE affects surface expression and/or release of cathepsin B, a cysteine protease that has been implicated in focal degradation of basement membrane.