Proteolytic Enzymes in Tumor Invasion and Degradation of Host Extracellular Matrices

Goldfarb, Ronald H.

doi:10.1007/978-1-4613-2635-9_21

Cited by 26 publications

(22 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most current models imply that proteases facilitate metastasis by degrading the basement membrane following their concentration at the cell membrane level or after their secretion [47]. We have obtained no evidence of this mechanism concerning cathepsin D, which is not concentrated on the cell membrane but is accumulated intracellularly in endosomes, lysosomes and some large acidic vesicles that are more frequently found in cancer cells than in normal mammary cells [42].…”

Section: Conclusion and Prospectsmentioning

confidence: 99%

See 1 more Smart Citation

Cathepsin D: A protease involved in breast cancer metastasis

1990

View full text Add to dashboard Cite

Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, via possibly saturation of the Man-6-P/IGF-II receptor, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in axillary node-negative tumors. Transfection of a human cDNA cathepsin D expression vector under the control of SV40 promoter increases the metastatic potential of 3YA1-Ad12 rat tumorigenic cells when intravenously injected into nude mice. The mechanism of cathepsin D-induced metastasis is currently unknown. These results indicate that overexpression of cathepsin D might facilitate breast cancer metastasis, suggesting new possible therapeutic approaches.

show abstract

Section: Conclusion and Prospectsmentioning

confidence: 99%

“…Neutral proteases should also play an important role in cancer metastasis [47,48]. However very few retrospective clinical studies have shown a high correlation between concentrations of these proteases in the primary tumor and the subsequent occurrence of metastasis.…”

mentioning

confidence: 99%

Cathepsin D: A protease involved in breast cancer metastasis

1990

View full text Add to dashboard Cite

show abstract

“…Proteases have long been thought to play a role in the invasion and metastasis of cancer cells which over-produce and secrete a series of different proteases, involved in a cascade of proteolytic events [17][18][19][20]. One major difficulty is to define from these enzymes (tissue and urokinase type plasminogen activator, collagenases, other metallo proteinases, cathepsins, elastase, etc...) which proteases are causally involved in human carcinogenesis.…”

Section: The 52k Protein Is a Secreted Pro-cathepsin Dmentioning

confidence: 99%

Cathepsin D in breast cancer

Rochefort

1990

Breast Cancer Res Tr

View full text Add to dashboard Cite

Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro-cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans and to activate other proteinases in acidic microenvironments. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in lymph node-negative tumors. These results suggest that overexpression and possible derouting of cathepsin D plays an important role in invasion and metastasis of breast cancer.

show abstract

“…Increased activity of these proteases has been noted in several pathological conditions. These include certain carcinoma (Goldfarb 1986;Rochefort et al 1987), muscular dystrophy (Kominami et at. 1987) and arthritis (Etherington et al 1988).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Cathepsin B, D, H and L Activity in Four Species of Pacific Fish

Porter

Koury

Stone

1995

J Food Biochemistry

View full text Add to dashboard Cite

The activities of cathepsins B, D, H and L were compared in crude muscle extracts from four species of fish: Pacific whiting (PW), (Merluccius productus); arrowtooth flounder (ATF), (Atheresthes stomias); Alaska pollock (AP), (Theragra chalcogramma); and Pacific cod (PC), (Gadus macrocephalus). Both PW and ATF are known to undergo softening during post‐mortem handling and cooking while AP and PC do not. Cathepsin B and L activities were both higher in extracts of PW and ATF than in AP and PC. Cathepsins B and L activities were both much higher in PW than in ATF. Cathepsin H activity was highest in AP followed by ATF with PC and PW having the lowest activities. Cathepsin D activity was extremely low in all four species. The heat stability of the various cathepsin activities showed cathepsin B to be the most heat labile and was inactivated by 50C heating for 15 min. Cathepsin H activity was inactivated at 60C, while cathepsin L required 70C for inactivation. Cathepsins B and L are the most likely responsible for softening in PW and ATF during holding and subsequent processing. However, during cooking, cathepsin L likely causes the most damage since it requires 70C for inactivation. The difference in heat stability of cathepsins B and L can be used to differentiate between their activities.

show abstract

Proteolytic Enzymes in Tumor Invasion and Degradation of Host Extracellular Matrices

Cited by 26 publications

References 119 publications

Cathepsin D: A protease involved in breast cancer metastasis

Cathepsin D: A protease involved in breast cancer metastasis

Cathepsin D in breast cancer

Comparison of Cathepsin B, D, H and L Activity in Four Species of Pacific Fish

Contact Info

Product

Resources

About