Inhibitory properties of low molecular mass cysteine proteinase inhibitors from human sarcoma

Lah, Tamara T.; Clifford, John L.; Helmer, Kent M.; Day, Nancy A.; Moin, Kamiar; Honn, Kenneth V.; Crissman, John D.; Sloane, Bonnie F.

doi:10.1016/0304-4165(89)90144-x

Cited by 51 publications

(29 citation statements)

References 22 publications

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“…As a result, in breast cancer, the cathepsin B and L activities were found to be much more increased than the respective protein levels, suggesting that the increase in activity was not entirely due to the induction of the respective proteins . The changes in molecular structure of inhibitors may decrease the binding affinity for the target enzymes, as described by Lah et al (1989) for stefin A in human sarcoma. In lung tumour tissue, cathepsin B was found to be more resistant to inactivation by E-64 than cathepsin B from control lung tissue (Křepela et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis

et al. 2004

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To determine the role of the cysteine proteinase inhibitor cystatin C in the invasive behavior of squamous cell carcinoma of the head and neck (SCCHN), Cystatin C protein level was measured in 82 pairs of primary tumour tissue and adjacent noncancerous mucosa, using the enzyme-linked immunosorbent assay. The median level of cystatin C in tumour tissue was 1.18 times lower than that in corresponding mucosa (P ¼ 0.031). In normal mucosa samples, the cystatin C level was influenced by the site of sampling: it was lower in nonlaryngeal tissue samples (oral cavity, oro-or hypopharynx) than in laryngeal samples (P ¼ 0.004). The tumour cystatin C level correlated inversely with pN-stage (P ¼ 0.047), whereas a trend of lower cystatin C levels was observed in the group with extranodal tumour extension compared to those with no extranodal spread (P ¼ 0.069). In univariate analysis, the patients with low tumour cystatin C levels exhibited poor disease-free survival (DFS, P ¼ 0.013) and disease-specific survival (DSS, P ¼ 0.013). In multivariate analysis, the most powerful predictor of survival was pN-stage (DFS: P ¼ 0.040, HR 2.78; DSS: P ¼ 0.011, HR 4.36,), followed by the cystatin C level (DFS: P ¼ 0.043, HR 0.22; DSS: P ¼ 0.067, HR 0.25). When comparing the prognostic strength of cystatin C to that of stefin A, another cysteine proteinase inhibitor, which emerged as the most significant prognosticator for survival in our previous study analysing the same cohort of patients, stefin A proved to be significantly more reliable predictor for both DFS and DSS than cystatin C. Our results indicate that cystatin C is implicated in the invasive behavior of SCCHN, and that there are variations in regulation of proteolytic pathways under nonmalignant conditions, inherent to individual subsites inside the upper aerodigestive tract. The correlation between high cystatin C levels and improved survival concurs with the concept of the protective role of high levels of cysteine proteinase inhibitors in tissue homogenates that has been previously suggested by the survival results in breast and lung carcinoma as well as SCCHN.

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Section: Discussionmentioning

confidence: 99%

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis

et al. 2004

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“…Similarly, decreased stefin A transcripts were observed in 4 of 5 breast carcinomas as compared to matched normal breast tissues (13). In addition to decreased amounts of stefin A in malignant tissues, Lah and coworkers (14,15) have shown that stefin A, isolated from human sarcoma tissue, has an altered inhibitory activity, being less effective than normal stefin A in inhibiting the proteolytic activity of both papain and cathepsin B. Lastly, we have demonstrated in murine tumors that there is an overall decrease of CPI activity accompanied with an enrichment of the activity within the plasma membrane fraction (16). Subsequent work established that the partially purified membrane-associated CPI activity of the highly invasive murine hepatoma, Hepa-cl9, is immunologically related to stefin A (17).…”

Section: Introductionmentioning

confidence: 89%

“…Inhibitory activity against papain was measured in a stopped assay according to the published protocol of Lah et al (14). Papain activity was assessed against the substrate Z-Phe-ArgNHMec.…”

Section: Assay Of Cpi Activitymentioning

confidence: 99%

Functional expression of recombinant human stefin A in mammalian and bacterial cells

Calkins

Dosescu

Day

et al. 2007

Protein Expression and Purification

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Recombinant human cysteine protease inhibitor, stefin A, was expressed in both E. coli and BSC-1 monkey kidney cells utilizing pET and recombinant Vaccinia virus systems, respectively. The expressed protein was purified and analyzed by SDS-PAGE and western blot analysis utilizing a polyclonal antibody against rat cystatin α. In both cases the purified protein appeared as a single band corresponding to the molecular weight of stefin A (~10 kDa). Viability of the expressed stefin A was determined by the inhibition of the plant cysteine protease, papain. Recombinant human stefin A expressed in both E. coli and BSC-1 cells was shown to almost completely inhibit papain. The expression of a fully functional recombinant human stefin A in the bacterial system provides a highly efficient tool for the production of large quantities of the protein. This can be an important tool in kinetic studies as well as in production of antibodies for other analytical studies (immunoblot, immunohistochemical studies, etc.). Expression in the mammalian cells on the other hand, can provide a significant research tool to study the functional roles of stefin A in the mammalian systems such as the regulation of cysteine proteases.

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Section: References Andmentioning

confidence: 99%

“…CPs activities are down-regulated by endogenous inhibitors, such as cystatins. Loss of expression and activity of certain members of the cystatin superfamily have been shown to correlate with the metastatic ability of some cancer cells (19)(20)(21).Epidemiological evidence suggests that low exposure to sunlight and vitamin D deficiency might be risk factors for prostate cancer mortality (22,23). Much research has focused on 1,25-VD, the active metabolite of vitamin D, and its ability Abbreviations: 1, 1a, ; CP, cathepsin; CPI, cathepsin inhibitor; ECM, extracellular matrix; HRPC, hormone refractory prostate cancer; MMP, matrix metalloproteinase; PA, plasminogen activator; PAI, plasminogen activator inhibitor; TIMP, tissue inhibitors of metalloproteinase; tPA, tissue PA; TPA, 12-O-tetradecanoylphorbol-13-acetate; uPA, urokinase PA. y These authors contributed equally to this work.…”

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confidence: 99%

To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination With Vitamin D, in Vitro and in Vivo

Lee¹

2006

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. (From -To) A summary of this proposal was the follow statement The incidence of prostate cancer has increased rapidly during the past decades and it has now become the most common malignancy of men in many Western nations. In the USA, prostate cancer represents the second leading cause of cancer death in men. ost prostate cancer initially responds to androgen ablation treatment, however, eventually it relapses to an androgen-independent state, leading to tumor outgrowth. Therefore, much effort is needed towards understanding the mechanisms involved in development and progression of prostate cancer and developing new strategies for its prevention and treatment. Results of recent epidemiologic and animal model studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), which prevent biosynthesis of prostagladins, biosynthesis through inhibition of COX activity, act as chemopreventative agents. We examined the expression of COX-2 in prostate cancer tissue arrays, which consist of normal, BPH, PIN, and low-and high-grade prostate tumor samples. In our preliminary study we found that COX-2 expression is significantly higher in cancer than in normal or BPH prostate samples and the tendency of COX-2 expression in prostate cancer cells is consistent with prostate cancer cell lines, implying COX-2 expression in prostate cancer might be up-regulated during cancer progression. Treatment of prostate cancer cells with a selective COX-2 inhibitor, NS-398, induces VDR expression, and thus might result in increasing the vitamin D sensitivity of such cells. In return, treatment of prostate cancer cells with 1,25-VD results in reduction of COX-2 mRNA expression, but not COX-1 expression. REPORT DATE (DD-MM-YYYY) 01-01-2006 REPORT TYPE Annual DATES COVEREDBased on the bi-directional regulation involving vitamin D and the COX-2 inhibitor, we hypothesize that combining vitamin D and a COX-2 inhibitor in the treatment of prostate cancer will be beneficial to the treatment of prostate cancer.In this proposal, we will examine the effects of combination of 1,25-VD, its analog (EB1089), and a COX-2 inhibitor NS-398, comp...

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Inhibitory properties of low molecular mass cysteine proteinase inhibitors from human sarcoma

Cited by 51 publications

References 22 publications

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis

Cysteine proteinase inhibitor cystatin C in squamous cell carcinoma of the head and neck: relation to prognosis

Functional expression of recombinant human stefin A in mammalian and bacterial cells

To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination With Vitamin D, in Vitro and in Vivo

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