Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel human cystatin gene was identified in a differential display comparison aimed at the isolation of transcriptionally regulated genes involved in invasion and metastasis of breast cancer. Messenger RNAs from primary and metastatic tumor cells isolated from the same patient were compared. A partial cDNA was isolated that was expressed in the primary tumor cell line but not in the metastatic line. The full-length cDNA was cloned and sequenced, and the inferred amino acid sequence was found to encode a novel protein, which we named cystatin M, with 40% homology to human family 2 cystatins and similar overall structure. Cystatin M is expressed by normal mammary cells and a variety of human tissues. The mature cystatin M protein was produced in Escherichia coli as a glutathione S-transferase fusion protein using the pGEX-2T expression system and purified by affinity chromatography. The cystatin M fusion protein displayed inhibitory activity against papain. Native cystatin M protein of approximately 14.5 kDa is secreted and was immunoprecipitated from supernatants of mammary cell cultures using affinity-purified antisera raised against recombinant cystatin M. An N-glycosylated form of cystatin M of 20-22 kDa was co-immunoprecipitated and accounted for about 30-40% of total cystatin M protein. Both forms of native cystatin M also occurred intracellularly. Consistent with the mRNA differential expression, no cystatin M protein was detected in metastatic mammary epithelial tumor cells. Loss of expression of cystatin M is likely associated with the progression of a primary tumor to a metastatic phenotype.
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PMID:Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer. 899 80

Lysosomal cysteine proteinases, also known as cysteine cathepsins (Cats), belong to the papain family of proteinases, and share a similar protein structure and mechanism of action. However, subtle structural differences between these cathepsins, e.g. Cats B, H and L, give rise to potentially important variations in substrate specificity and differences in inhibition by their endogenous inhibitors, the cystatins, stefins and kininogens, under physiological and pathological conditions. Alterations in expression of Cat B and Cat L have been observed at various levels in malignant human tumor tissue compared to normal and benign tissue counterparts. We proposed that an imbalance between cathepsins and cystatins, associated with the metastatic tumor cell phenotype, may facilitate tumor cell invasion and metastasis and be responsible for early relapse of the disease after removal of the primary tumor. The results of our initial investigations on cysteine cathepsins and their endogenous inhibitors in human breast, lung and head and neck carcinomas, as well as in body fluids of melanoma and colorectal carcinoma bearing patients, have indeed shown their high prognostic impact for the survival of these patients.
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PMID:Cysteine proteinases in cancer progression and their clinical relevance for prognosis. 952 63

In this monograph, the chemopreventive effects of enterally administered proteases (trypsin, chymotrypsin, and papain) have been documented in a series of animal experimental tumor models. The experimental evidence demonstrates a significant inhibition of growth of both the primary tumor and the metastatic disseminations. Survival in animals treated with proteases is significantly longer than in untreated animals. The results confirm the fundamental correlation between early initiation of therapy and consequent growth of the tumorous disease. Comparable results have been shown in solid tumors in animal models (melanoma and Lewis lung carcinoma) and in human tumors (pancreatic and breast cancers). In this article, details of the known mechanisms of systemic actions of enterally administered proteases are documented and their relationship with cancerogenesis is discussed.
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PMID:Exogenous proteases confer a significant chemopreventive effect in experimental tumor models. 1911 25