Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-five breast cancer specimens were processed as part of a program in tumor acquisition, propagation, and preservation for biotherapy. Nine long-term culture cell lines were developed. Four cell lines were from solid tumor metastases, two lines were from pleural fluid specimens, and three were from xenograft tumors grown in nude mice. Two of the xenograft-derived cell lines were from biopsies which produced tumor cell lines as well. Success in establishing cultures did not correlate with the viability of the biopsy received. Poor tumor cell attachment to culture plastic was the most common problem. For certain specimens, attachment and growth were enhanced on collagen and extracellular matrix substrates. Collagen was beneficial in the development of one cell line. The cell lines were characterized and each of the lines contained more nuclear DNA than found in normal cells. Four of five lines tested were tumorigenic in nude mice. Five of nine were clonogenic in soft agar. Each of the cell lines tested reacted with at least two anti-tumor monoclonal antibodies. Xenograft and biopsy-derived cell lines from the same tumor were similar in their characteristics. While breast cancers are indeed difficult to establish and propagate in culture, the use of xenografts and special substrates appears to be beneficial in the development of cell lines from some tumors.
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PMID:Cultured cell lines from human breast cancer biopsies and xenografts. 209 90

Metalloproteinases secreted by tumor cells play an important role in metastasis. In the present study, we determined whether an inhibitor of these proteinases could inhibit the ability of tumor cells to degrade collagen and to metastasize. Metalloproteinases with degradative activities for type I collagen, type IV collagen, gelatin, and casein were secreted by a highly metastatic rat embryo cell line (4R) transfected by c-Ha-ras1 (also known as HRAS1). These metalloproteinases were identified by sodium dodecyl sulfate substrate-polyacrylamide gel electrophoresis as 92-kilodalton and 68-kilodalton gelatinolytic enzymes and 48-kilodalton and 45-kilodalton caseinolytic proteinases. A recombinant human tissue inhibitor of metalloproteinases (rTIMP) completely inhibited the proteolytic activities of these enzymes and was also a potent inhibitor of the proteolytic degradation of collagen by intact c-Ha-ras1-transfected cells. The ability of these cells to colonize the lungs after intravenous injection into nude mice was inhibited by 83% when rTIMP was repeatedly injected intraperitoneally into the animals. These data demonstrate that rTIMP is a potent inhibitor of the metalloproteinase activities of these cells and can also inhibit their metastatic potential.
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PMID:Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. 215 82

Production of type IV collagenase by tumor cells has been linked to their metastatic potential in several experimental models. A possible role for this enzyme in basement membrane type IV collagen turnover has also been suggested. Two recently developed affinity-purified, monospecific antibodies directed against the amino terminus (H1), or an internal active site domain (metal binding region [MBR]) of human type IV collagenase, were employed in the avidin-biotin-immunoperoxidase technique in formalin-fixed, paraffin-embedded breast tissue samples from 55 patients. Intense cytoplasmic immunostaining of myoepithelial cells was found in normal and hyperplastic tissue, and discontinuous staining was noted in intraductal carcinomas. Luminal epithelial cells were negative or weakly positive in large- or medium-sized ducts but reacted frequently in normal terminal ducts and hyperplastic lesions. Epithelial cells in intraductal carcinomas exhibited immunoreactivity in 20 of 23 cases. Invasive carcinomas were positive in 36 of 40 cases, and metastatic cells in lymph nodes stained in 10 of 12 cases. These results support a role for type IV collagenase in the basement membrane remodeling of normal breast. Our findings suggest that myoepithelial cells play a pivotal role in this enzymatic activity. The high percentage of positive cells in invasive carcinomas and the strong immunoreactivity of lymph node metastases support the role of the enzyme in tumor invasion and metastasis and suggest that tumor cells are the essential source of the enzyme in these processes.
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PMID:Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. 215 30

We studied 28 lung carcinomas representing different histological types and three of their regional lymph node metastases immunohistochemically by using specific antibodies against two basement membrane proteins--the 7S domain of type IV collagen and the P1 fragment of laminin. One feature common to all peripherally growing tumors, regardless of the histologic type, was an intact basement membrane between the tumor and the unaffected lung tissue. At these locations, the basement membrane was organized into alveolar structures that did not differ from normal lung tissue. The fibrotic central areas of the tumors did not exhibit this phenomenon. Based on these findings, we believe that malignant tumors of the lung utilize preserved alveolar basement membranes for their local spread. This finding seems to represent a general property of all lung carcinomas, not only adenocarcinomas of the bronchiolo-alveolar type.
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PMID:Immunohistochemical evidence that lung carcinomas grow on alveolar basement membranes. 215 43

Type IV and interstitial collagenolytic activities were compared in human malignant and normal trophoblast cells cultured on plastic, in presence or absence of laminin in solution, on matrigel (a gel of basement membrane components) and on type I collagen gel. Laminin highly stimulated the type IV collagenolytic activity but not the interstitial collagenolytic activity, in malignant trophoblast cells. This glycoprotein had no effect on the interstitial collagenolytic activity and doubled the type IV collagenolytic activity in normal trophoblast cells. Thus malignant trophoblast cells produce preferentially the enzyme able to degrade basement membrane when in contact with laminin, and the enzyme able to degrade interstitial collagen fibers when cultured on type I collagen. On the contrary, type I collagen gel and matrigel equally increased both type IV and interstitial collagenolytic activities by normal trophoblast cells. Interactions of tumor trophoblast or normal trophoblast cells with the extracellular matrix result thus in distinct stimulations of collagenolytic activities. Increased production of type IV collagenolytic activity upon exposure to laminin appears to be specific of the metastatic phenotype.
Invasion Metastasis 1990
PMID:Type IV and interstitial collagenolytic activities in normal and malignant trophoblast cells are specifically regulated by the extracellular matrix. 215 47

The activity of serum type IV collagen-degrading enzyme was measured in 21 patients with hepatocellular carcinoma, and the changes in the enzyme activity were investigated with respect to metastasis. The activity of serum type IV collagen-degrading enzyme did not increase until tumor invasion to the portal vein and intrahepatic metastasis were clearly detected ultrasonographically. Activities did not increase during the observation period in patients whose tumor grew slowly and did not invade the portal vein. Thus, the enzyme activity increases in relation to the metastasis of hepatocellular carcinoma and may be useful to detect ongoing metastases.
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PMID:Elevation of serum type IV collagen-degrading enzyme in hepatocellular carcinoma with metastasis. 216 99

In order to investigate the role of collagenase in cancer invasion and metastasis, two collagenase activities of interstitial collagenase and type IV collagen degrading enzyme (type IV collagenase) were determined in 40 cases of human stomach cancer tissue. Elevated cancers which are known to have a propensity to cause blood-borne metastases showed higher activities of both interstitial collagenase and type IV collagenase than flat or ulcerous type of cancer. Using the parameters of lymph node metastasis vs tumor size or vs depth of cancerous invasion into the stomach wall, classification of the cases was attempted according to the degree of malignancy. In the cases with marked lymph node metastases in spite of small tumor size and/or shallow cancerous invasion into the stomach wall, type IV collagenase activity was higher than that in the cases with lower malignancy (p less than 0.025, p less than 0.05, respectively). These results suggest that collagenase in stomach cancer tissue play an important role in the invasion and metastasis of cancer cells. Type IV collagenase activity in stomach cancer tissue could be one of the useful biological markers for the degree of malignancy.
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PMID:The collagenase activities, interstitial collagenase and type IV collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis. 217 1

The processes of cell adhesion and active spreading were assessed between frog normal pronephric, pronephric tumor and heterologous liver cells. Confluent monolayers were developed on collagen-coated microcarrier beads, then exposed to homologous or heterologous cells and cultivated with a rotary (orbital) flask culture technique at 23 degrees C. All three cell lines attach and actively spread on the collagen-coated microcarrier beads. Secondary attachment of normal (non-transformed) proliferating cells to their confluent monolayers occurs but cell spreading is restrained. Dissociated pronephric tumor cells adhere and actively spread on the surfaces of normal pronephric cells, and eventually encapsulate them. Normal pronephric cells do not adhere readily to the cell surfaces of pronephric tumor cells grown on microcarrier beads. Tumor cells also attach, actively spread and overgrow heterologous liver cells attached to microcarrier beads. Suboptimal temperatures (17 degrees C) slow tumor cell attachment and spreading on normal cells. Colder temperature (8 degrees C) permits tumor cell attachment and adhesion to normal cell-coated beads but active cell spreading is prohibited. The same temperature retards cell spreading directly on the collagen-coated beads.
Clin Exp Metastasis
PMID:Adhesion of frog pronephric tumor cells to normal cells cultivated on microcarrier beads. 218 59

Tumor metastasis is the major cause of death of oncology patients. One of the characteristic properties acquired by the metastatic cell is the ability to cross basement membranes. These are compartments of extracellular matrix composed largely by collagen type IV, laminin and a heparan sulphate proteoglycan. Here we review the use of a reconstituted basement membrane (Matrigel) in the Boyden chamber assay (Chemoinvasion Assay) for the assessment of the invasiveness of tumor cells of human origin. The possibility of using this test for the rapid evaluation of human tumor specimens from operated patients is discussed.
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PMID:[Use of reconstituted basal membranes for the study of invasion of human tumor cells: current status and future prospects]. 220 33

Sixty-seven adult walleye fish were examined by light and transmission electron microscopy. The fish were affected by a mesenchymal tumor previously termed Walleye Dermal Sarcoma that commonly affects up to 27% of the population seasonally. Biopsies from 24 fish were collected, and complete postmortem examinations were performed on 43 fish. Grossly, the tumors had the appearance of randomly distributed, often clustered, spherical nodules, 2-5 mm in diameter with a smooth and often ulcerated surface. The tumors arose from the superficial surface of scales and consisted of fibroblast-like cells separated by a moderate amount of collagen (43/67) or osteoid material (24/67). Lymphocytic infiltration (28/67) associated with vacuolar degeneration of tumor cells (28/67) and centrally located coagulation necrosis (30/67) were observed. Although tumor cells were often highly anaplastic, no local invasions or metastases were present. In contrast with previous descriptions of this tumor, no viral particles could be observed electron microscopically. The variably anaplastic appearance of the tumor, its biological behavior, and its restriction to dermis are features in common with canine cutaneous histiocytoma and equine sarcoid. The multicentric origin, the restriction to the dermis, and the absence of invasion or metastases of Walleye Dermal Sarcoma differ from retrovirus-induced avian and murine sarcomas that arise locally, that invade, and that often metastasize.
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PMID:Histologic and ultrastructural studies of dermal sarcoma of walleye (Pisces: Stizostedion vitreum). 223 87


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