Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients.
Cancer Res 1989 Dec 15
PMID:Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure. 258 33

A chromosomal analysis was performed on two cell lines which were derived from the liver of two rats exposed to diethylnitrosamine in vivo. The cells were obtained by collagenase perfusion of the liver at an early stage of development of ATPase-deficient putative preneoplastic populations, and propagated from foci of epithelial cells which started growth in vitro. Cell line CL 38 proved to be tumorigenic after transplantation into nude mice, giving rise to hepatocellular carcinomas and metastases. Cell line CL 44 was nontumorigenic after transplantation into nude mice and was therefore considered preneoplastic. The diploid nontumorigenic line CL 44, with a modal number of 42 chromosomes, showed a deletion of chromosome 1 and a translocation of chromosomes 3 and 14 [t(3q12;14q21)]. The hyperdiploid neoplastic cell line CL 38 has a modal chromosome number of 52 and showed tri- or tetrasomy of chromosomes 3, 7, 9, 11, and 12 and a marker chromosome that might have originated from aberrant chromosome 1. One or two homologues of chromosome 3 showed terminal deletions (q42, q41, or q35). In both cell lines rearrangements of chromosome 11 were observed [rob(11q;?) or +11 or -11 or del(11)(q12)]. Some of these karyotype abnormalities are located on the same chromosome as described for transplantable hepatomas and for other chemically induced tumors of the rat.
Cancer Res 1989 Jun 01
PMID:Chromosomal analysis of a diethylnitrosamine-induced tumorigenic and a nontumorigenic rat liver cell line. 272 Jun 63

Cysteine proteinases, particularly cathepsins B and L, have been strongly implicated in fostering metastasis in mice. In this work four different inhibitors of cysteine proteinases have been shown to inhibit the invasion of the human amnion by murine melanoma and mammary carcinoma cells in vitro. Two of the inhibitors are synthetic peptides [ZPhePheCHN2 (benzyloxycarbonyl-L-phenylalanyl-L-phenylalanyldiazomethane) and ZPheAlaCH2F [3-(N-benzyloxycarbonylphenylalanylamido)-DL-1-fluoro-2-butanone]] and two are thiol protease inhibitors (TPIn, TPId) isolated from the skeletal muscle of the hind limbs of normal and dystrophic mice, respectively. The inhibitors (ZPhePheCHN2, TPId), with apparent selectivity for cathepsin L, blocked invasion as effectively as inhibitors (ZPheAlaCH2F, TPIn) effective on both cathepsins. The data reveal that in these cell lines the cysteine proteinases contribute significantly to the invasive capacity of the cells, but to a lesser extent than do the metalloproteinases. We suggest that the cysteine proteinases facilitate the action of metalloproteinases (collagenase, gelatinase, and stromelysin), possibly by activating them, by inactivating the tissue inhibitor of metalloproteinases, and/or by making basement membrane matrix more accessible.
Cancer Res 1989 Jul 01
PMID:Suppression by cathepsin L inhibitors of the invasion of amnion membranes by murine cancer cells. 273 Nov 77

A short-term in vivo method for assay of repair and replication of rat liver DNA has been developed, by which possible hepatocarcinogens could be identified in a few days. F344 rats were treated orally with two genotoxic hepatocarcinogens, dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2AAF), or a nongenotoxic hepatocarcinogen, carbon tetrachloride (CCl4). Then at suitable times after treatment, their hepatocytes were isolated by a two-step collagenase perfusion technique in situ and incubated with [3H]dThd with or without hydroxyurea, which inhibits DNA replication. Their nuclear DNA was then extracted and the incorporation of [3H]dThd into nuclear DNA was determined in a liquid scintillation counter. Unscheduled DNA synthesis (DNA repair), induced by DMN at doses of 2.5-10 mg/kg body weight and by 2AAF at doses of 12.5-50 mg/kg body weight, could be detected 2 h and 4 h after their administration as an increase of DNA synthesis of up to 5.8-fold and 6.0-fold, respectively, in the presence of hydroxyurea. Replicative DNA synthesis, induced by CCl4 at a dose of 200 mg/kg body weight, could be detected 48 h after its administration as a 23-fold increase of DNA synthesis in the absence of hydroxyurea and was inhibited approximately 97%-99% by hydroxyurea. Replicative DNA synthesis induced by 2AAF at a dose of 25 mg/kg body weight 16 h after its administration could be detected as a 6.8-fold increase of DNA synthesis in the absence of hydroxyurea. These results show that unscheduled and replicative DNA synthesis can be clearly distinguished by simultaneous measurements of the incorporation of [3H]dThd into nuclear DNA in the presence and absence of hydroxyurea.
J Cancer Res Clin Oncol 1989
PMID:In vivo short-term assays of repair and replication of rat liver DNA. 276 99

The objective of this study was to determine whether DNA synthesis induced in the livers of female rats treated with ethinyl estradiol (EE) was due to direct effects of this synthetic estrogen on hepatocytes. Hepatocytes, obtained by collagenase perfusion from female Lewis rats, were cultured in serum-free medium containing low or no phenol red and supplemented with insulin, transferrin, and selenium. When present at 10-15 microM for the initial 30 h of culture, EE caused a subsequent 2-2.7-fold increase in hepatocyte DNA synthesis. Pretreatment of the hepatocytes with EE during the first 30 h of culture caused an EE concentration-dependent enhancement of their subsequent DNA synthetic response to epidermal growth factor (EGF). Pretreatment with EE shifted the EGF dose-response curve, causing a dramatic enhancement of the response to EGF beginning at 2 ng EGF/ml. The response to a saturating (25 ng/ml) dose of EGF was also greatly enhanced. Determination of the effect of EE on hepatocyte surface EGF receptors revealed that the increased responsiveness of DNA synthesis to EGF was accompanied by a twofold increase in EGF receptor number per cell. These results indicate that EE has direct, growth-related effects on hepatocytes which may contribute to liver growth induced in vivo by this tumor promoter.
Cancer Res 1989 Jul 01
PMID:Effects of the liver tumor promoter ethinyl estradiol on epidermal growth factor-induced DNA synthesis and epidermal growth factor receptor levels in cultured rat hepatocytes. 278 53

Nylon-wool-eluted lymphocytes, isolated from a site of tumor rejection in Balb/c mice expressing concomitant tumor immunity, were examined for their ability to inhibit the growth of the EMT6 tumor. Tumor growth inhibition was monitored after co-inoculation of lymphocytes and tumor cells into naive mice in a Winn-type adoptive-transfer assay. A pre-implanted gelatin sponge was employed to capture the tumor-infiltrating lymphocytes. Mice harboring primary tumors were implanted 8 days later with gelatin sponges. The pre-implanted sponges were then inoculated with a secondary tumor challenge 2 days after implantation of the sponge (i.e. 10 days after primary tumor challenge). On day 17 (7 days after secondary tumor challenge), the immune sponges were retrieved, digested in collagenase and the T lymphocytes were isolated using a nylon-wool column. Blank sponges (lacking tumor cells), obtained from primary-tumor-bearing or non-tumor-bearing animals, were included for comparison. The data showed that T lymphocytes isolated from immune sponges inhibited tumor growth while T lymphocytes recovered from blank sponges did not. At an effector:target (E:T) ratio of 10:1 the lymphocytes from the immune sponges were able to prevent totally the growth of tumors in all cases (100% inhibition). This ability was reduced (60% inhibition) at an E:T ratio of 1:1. Comparison of the antitumor activities of the immune-sponge-derived cells with those from the spleen of the same animal revealed the superiority of the former. Depletion of immune-sponge-derived cells with anti-Thy1.2, anti-Lyt2.2 or anti-L3T4 and complement resulted in a marked decrease in tumor-inhibitory activity. These results indicate that T lymphocytes, expressing Thy1.2, Lyt2.2 or L3T4 antigens, are involved in conferring protection to Balb/c mice against the EMT6 tumor.
Cancer Immunol Immunother 1989
PMID:Implantation of a gelatin-sponge as a model for effector recruitment. Tumor growth inhibition by T-lymphocytes recovered from a site of tumor rejection. 278 57

Recent studies of murine tumor models and certain human tumor cell lines have provided evidence for intratumor heterogeneity in expression of extracellular matrix receptors and in the elaboration of matrix-degrading enzymes. However, little is known about possible intratumoral heterogeneity in the production of matrix macromolecules. We have, therefore, examined the biosynthesis and secretion of matrix proteins by cells derived from a polyclonal human cell line (JH-17) established from a large cell undifferentiated carcinoma of the lung. For the present studies, we focused on the production of collagens and structural glycoproteins by two phenotypically different aneuploid clones, designated C13 and C22. These clones were distinctive in their inability to grow in soft agar or to form tumors in nude mice and had identical DNA contents. Tumor cells were labeled with [3H]proline and the newly synthesized proteins accumulating in the culture medium were identified using biochemical and immunologic techniques. Clone C13 secreted at least three genetically distinct collagens, including type V procollagen (PC), type IV procollagen, and a type VIII-like collagen. By contrast, the clone C22 synthesized fibronectin, and a single bacterial collagenase-sensitive and pepsin-resistant component consistent with type I trimer. These studies emphasize the potential diversity of matrix proteins synthesized by neoplastic cells and suggest that there is intratumoral heterogeneity in matrix protein biosynthesis in vivo. These studies further suggest that tumor-derived matrix may be altered during tumor progression or cell selection in vivo.
Cancer Res 1987 Nov 15
PMID:Heterogeneity in the production of collagens and fibronectin by morphologically distinct clones of a human tumor cell line: evidence for intratumoral diversity in matrix protein biosynthesis. 282 40

During cell proliferation, several "factors" are released into the microenvironment, or culture medium. The experiments described sought and examined agents that may cause or support malignant cell transformation. The response of colon cells from patients with ulcerative colitis (UC), familial polyposis coli (FPC) and colon carcinoma (CCC) to these agents was monitored by carcinoembryonic antigens (CEA) released into the medium during cell proliferation in a serum-free hormone-defined (SFHDM) medium, oncogenicity in athymic mice and colonigenicity, i.e. the ability of the cells to form colonies in soft agar. When cultured on the extracellular matrix (EM), i.e. footprints from colon carcinoma cells (short term or established cell lines), and in SFDHM, colon cells from patients with UC and FPC showed significant (P = 0.001) increases in all the three parameters. Analyses indicated that EM from cultures of [35S]methionine-labelled normal epithelial colon cells (NCE) differed from those left by UCC, FPC and CCC cell cultures. EM from NCE cell cultures did not contain [35S]methionine-labelled glycoproteins resistant to collagenase action which were not fragments of fibronectin, and which were present in EM from CCC cells. It is concluded that the extracellular matrix from malignant colon cells contains agents that support colon cell oncogenic transformation.
Eur J Cancer Clin Oncol 1987 Jul
PMID:Ulcerative colitis and familial polyposis oncologic transformation to colon carcinoma: changes in carcinoembryonic antigen release. 282 26

A continuous line of human breast carcinoma cells, VHB-1, was established in culture following collagenase treatment of an infiltrating duct cell carcinoma. The cells displayed an epithelial pattern and multiplied rapidly. Maintained in monolayer culture, the VHB-1 cells exhibited a 30-h doubling time and a plating efficiency of 20%. The cells possessed an abnormal karyotype with a mode of 70-74 chromosomes per cell. The karyotype was heavily rearranged and numerous marker chromosomes were found. Transplantation of the cells into nude mice produced tumors bearing histological resemblance to the original material. The VHB-1 cells contained significant levels of prolactin receptors, were steroid hormone (estrogen, progesterone, androgen, glucocorticoid) receptor positive, and were capable of functional differentiation in vitro. These characteristics make the VHB-1 cell line a suitable model for studying the biological properties of human breast tumors.
J Cancer Res Clin Oncol 1987
PMID:Establishment and characterization of a new cell line (VHB-1) derived from a primary breast carcinoma. 282 20

Stromelysin is a collagenase-related connective-tissue-degrading metalloproteinase. We have detected RNAs capable of hybridizing to a rat stromelysin cDNA in 11 of 69 human tumours tested. Molecular cloning of cDNAs to these RNAs has identified them as a mixture of stromelysin RNA and a transcript of a hitherto-undescribed related human gene, the stromelysin-2 gene. We have also isolated cDNAs corresponding to a more distantly related new human gene, the pump-1 gene. A comparison of the cDNA-derived amino acid sequences of stromelysin-2 and pump-1 with the known sequences of stromelysin and collagenase reveals significant similarities, with conservation of sequence motifs believed to have functional importance in metalloproteinase action. We conclude that the collagenase gene family in humans consists of at least four members, and speculate that expression of these genes plays a role in cancer.
 ...
PMID:The collagenase gene family in humans consists of at least four members. 284 64


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