Inhibitors of cathepsins B and L induce autophagy and cell death in neuroblastoma cells.

This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to their ability to inhibit the activity of the isolated enzymes.

Understanding and recognizing the Pelger-Huët anomaly.

The Pelger-Huët anomaly (PHA) is a recognized morphologic variant affecting all granulocytes but is most evident in polymorphonuclear neutrophils (PMNs). PHA is caused by a decreased amount of the lamin B receptor (LBR). Recognition of PHA morphologic features serves as a marker for mutations in the LBR gene.

Induction of cell death in neuroblastoma by inhibition of cathepsins B and L.

A specific irreversible inhibitor of both cathepsins B and L, Fmoc-Tyr-Ala-CHN(2) (FYAD) induced apoptosis of neuroblastoma cells but not other tumor cells. Cysteine protease inhibitors that were not efficient inhibitors of both proteases did not cause death of any cell line tested. Apoptosis was preceded by accumulation of large electron dense vesicles and multivesicular bodies in the cytoplasm.

Control of precerebellar neuron development by Olig3 bHLH transcription factor.

The rhombic lip (RL) is the neuroepithelium immediately adjacent to the roof plate of the fourth ventricle, and it gives rise to various brainstem and cerebellar cell types. Our study shows that the bHLH (basic helix-loop-helix) transcription factor Olig3 is expressed in the progenitors of RL, and ablation of Olig3 significantly affects the development of RL. In Olig3-/- caudal RL, the expression level of Math1 in the dorsal interneuron 1 (dI1) domain is reduced, and the formation of four mossy-fiber nuclei is compromised; dI2-dI3 neurons are misspecified to dI4 interneurons, and the climbing-fiber neurons (inferior olive nucleus) are completely lost.

Matrigel influences morphology and cathepsin B distribution of prostate cancer PC3 cells.

Increases in expression and activity of matrix-degrading enzymes such as the cysteine proteinases cathepsins B and L, and abnormal levels of their inhibitors, the cystatins, are associated with tumor cell invasion and metastasis. Environmental conditions have been shown to be causative factors in the development of a metastatic/invasive phenotype. We hypothesized that cell-matrix interactions affect the expression and activity of cathepsins B and L and their inhibitors in the prostate cancer cell lines, PC3 and DU145.

Increased cell density decreases cysteine proteinase inhibitor activity and increases invasive ability of two prostate tumor cell lines.

The ability of a cancer cell to metastasis to a distant site is partly dependent on the secretion of matrix degrading enzymes. The lysosomal cysteine proteinases, cathepsins B and L, have been shown to be secreted by a number of cancer cells and have been implicated in metastasis. Cathepsins B and L are regulated by a class of inhibitors known as the cystatins; aberrant cystatin activity has also been shown in a number of cancer cells.