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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Chromosomal analysis of a diethylnitrosamine-induced tumorigenic and a nontumorigenic rat liver cell line. 272 Jun 63

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.
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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

The invasion by malignant cells through extracellular matrix is an important part of the metastatic process, providing access to points of dissemination. Cell migration in tissues, however, depends not only on the destruction of extracellular matrices, but also on the locomotory behavior of the cells themselves. A quantitative study of aspects of cell behavior related to invasiveness was made using cellulose nitrate filters, both unimpregnated and filled with collagen, as models for some aspects of basement membrane. The relative penetration of mouse malignant cells into filters correlated with their spontaneous metastatic potential. Penetration of collagen-impregnated filters was greater than in unfilled filters. Pretreatment with collagenase enhanced the penetration of some cells into both collagen-impregnated and unfilled filters, and enhanced their motility on a plastic substrate; other cells showed enhanced penetration when incubated on collagenase-pretreated filters and no change in motility on the plastic substrate when incubated in collagenase-containing medium. These results emphasize the variability in response of different malignant cell types to factors present in the tumor environment and suggest that the effect of collagenase during invasion may be to enhance cell motility as well as to degrade the extracellular matrix.
Invasion Metastasis 1987
PMID:Collagenase effects on cancer cell invasiveness and motility. 282 98

We analyze here recent data from literature concerning the role of collagenases in cancer. The alteration of basement membrane (BM) and extracellular matrix components, in particular collagens, has been widely reported during tumor invasion. The collagenases degrade interstitial collagens (types I and III) and BM collagens (type IV). So, they break natural barriers and allow tumor cells to spread in surrounding tissues and metastasize. Classical collagenases are not able to degrade type IV collagen (the main component of BM) which, however, often appears to be very altered around tumor cells. Therefore, the existence of a specific type IV collagenase is necessary to explain this phenomenon. Most studies performed with the object of proving the role of collagenases in tumor invasion and metastasis have shown the presence of a type I collagenase, but type IV collagenase has been more difficult to evidence.
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PMID:[Collagenases and cancers]. 285 69

Prediction of early metastases in individual patients has been attempted by combined evaluation of a battery of recognised parameters such as blood vessel invasion (BVI) of tumor cells, Barr body frequency (BBF), plasminogen activator (PA), collagenase, estradiol receptors (ER), progesterone receptors (PgR), and peroxidase activity (PRA) in 18 malignant and 3 benign (control) breast tumors. Since breast tumor cells spread through the blood vessels, the cases were divided into BVI (+) and BVI (-) groups. Results show that in the former group, all the cases had poor prognosis and two even had distant metastases within one year. In BVI (-) group, 9 out of 12 appeared to have good prognosis.
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PMID:Prediction of biological behaviour of human breast cancer using multiple parameters. A preliminary study. 299 51

Bis(5-amidino-2-benzimidazolyl)methane (BABIM) is a synthetic aromatic amidine compound which has a number of important biochemical effects, including inhibition of a family of esteroproteases (trypsin, urokinase, plasmin) previously linked to the complex process of tumor invasion. Previous work has suggested that exogenous natural protease inhibitors can block invasion of tumor cells across basement membranes (BM) in vitro. The authors studied the effect of BABIM on the human cell line HT-1080 with the use of a quantitative in vitro amnion invasion assay system. They have verified the ability of these cells to grow in nude mice and metastasize via the lymphatics or blood vessels on the basis of the route of administration of the inoculum. Cells which were able to actively cross the entire BM were trapped on filters and counted by both brightfield microscopy and by beta scintillation counting of cells whose DNA was labeled with tritiated thymidine. In agreement with either counting technique, BABIM, at a concentration of 10(-4) M, significantly inhibited invasion (P less than 0.005) over the 7-day course of the experiments. Under these conditions, the inhibitor was nontoxic and did not alter the attachment of the cells to the amniotic membrane. Furthermore, a highly significant inhibition of invasion (P less than 0.001) was also demonstrated across a variation in molar concentration of BABIM of more than 2 orders of magnitude. Most remarkably, cells were initially inhibited in their ability to invade in the presence of between 10(-9) and 10(-3) M BABIM. Measurement of Type IV specific collagenase in media from these cells shows a significant inhibition of activity in the presence of BABIM. These results suggest two, not necessarily exclusive, alternative interpretations: first, that inhibition of the proteolytic steps along the pathway of activation of basement membrane degrading enzymes results in inhibition of invasion; second, that arginine directed esteroproteases may work in concert with cellular collagenolytic metalloproteinases in the process of invasion by human tumor cells through native matrix barriers.
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PMID:In vitro inhibition of human sarcoma cells' invasive ability by bis(5-amidino-2-benzimidazolyl)methane--a novel esteroprotease inhibitor. 300 61

The role of collagenolytic enzymes in tumor invasion and metastasis has been emphasized, but the source of enzyme activity has remained unclear. Degradation of stromal connective tissue is a common feature of invasive neoplasia, and host-tumor cell interactions are probably important for localized collagenolysis. We have examined the role of mast cells in malignant cell invasion using cells derived from the rat mammary adenocarcinoma 13762NF. Histologic studies have shown increased numbers of mast cells at the zone of tumor invasion. Mast cell products and conditioned medium from such cells stimulated the production of collagenolytic enzymes by stromal fibroblasts as well as certain subpopulations of tumor cells in vitro. The tumor cell response to mast cell-mediated stimulation of collagenolysis appears to be related to the metastatic potential of the tumor cell. A subpopulation of host fibroblasts derived from the invading tumor zone was also found to be more responsive to mast cell factors than normal fibroblasts, as judged by collagenase production. Thus the mast cell has the potential to induce collagenolytic activity from both host fibroblasts and tumor cells.
Clin Exp Metastasis
PMID:Host-mediated effectors of tumor invasion: role of mast cells in matrix degradation. 301 78

We have shown previously that an increase in tumor invasion and metastases occurred concurrently with a decrease in collagen content of the extracellular matrix surrounding the C3H mouse mammary adenocarcinoma borne by C3H/HeJ mice. In this paper we report the production of collagenase and elastase activities by the primary tumor cultures and three types of cloned C3H mouse mammary adenocarcinoma cell cultures. The primary tumor cell cultures and tumor-associated stromal cultures produced large amounts of collagenase and elastase activities. On the other hand, the primary tumor capsule cultures produced little or no collagenase and elastase activities even though they produced type I collagen. The production of proteases by the primary tumor cultures decreased along with time and with an alteration in the morphology of cell populations and/or passage of the cultures. The three clones of tumor cell cultures produced variable amounts of collagenase in response to induction by phorbol myristate acetate, an agent that stimulates maximal collagenase production. In contrast, all three cloned cultures elaborated significant amounts of elastase that degraded insoluble ligamental elastin, and most of the elastase production was increased further in response to induction by phorbol myristate acetate. Each cloned cell population exhibited differences in their production of collagenase and elastase in parallel with their difference in growth kinetics, yet these cells still possess the distinctive properties of the tumor. However, a unit amount of collagenase produced by each of the cloned cultures, with or without induction by phorbol myristate acetate, was less than that of the primary tumor cultures. Results suggest that some cell types or combination of cell types in the heterogeneous cell population of the tumor and/or their products appear to be responsible for the increased production of collagenase and elastase activities and for the invasiveness of a malignant tumor.
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PMID:Collagenase and elastase production by mouse mammary adenocarcinoma primary cultures and cloned cells. 302 19

Activated ras oncogene transfection into suitable recipient cells has been shown to induce the metastatic phenotype (Thorgeirsson, et al., Mol. Cell. Biol., 5: 259-262, 1985). We have used this model system to study the correlation of basement membrane collagenolysis with metastatic propensity. The c-Ha-ras oncogene alone, or combined with v-myc, transfected into early passage rat embryo fibroblasts, induce these cells to secrete high levels of type IV collagenolytic metalloproteinase and to concomitantly exhibit a high incidence of spontaneous metastases in nude mice. Cotransfection of c-Ha-ras plus the adenovirus type 2 E1a gene yields cells which are highly tumorigenic but nonmetastatic and fail to produce type IV collagenase. This effect is due to a suppression of collagenase elaboration, not increased production of a collagenase inhibitor, and not decreased production of a collagenase activator. The characteristics of the collagenase are identical to tumor type IV collagenase described previously. The nonmetastatic cells which failed to produce type IV collagenase retain the ability to secrete high levels of plasminogen activator. Transfection with the protooncogenic forms of Ha-ras or mos, or spontaneous transformation of NIH 3T3 cells or chemical transformation of BALB 3T3 cells yields cells which fail to produce collagenase, are tumorigenic, but totally nonmetastatic. These data support a biochemical linkage of type IV collagenase expression with the metastatic phenotype in this rodent system.
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PMID:Secretion of type IV collagenolytic protease and metastatic phenotype: induction by transfection with c-Ha-ras but not c-Ha-ras plus Ad2-E1a. 302 10

The myoepithelial-type cell line, Rama 712, derived from a normal rat mammary gland, deposits an extracellular matrix containing type-IV collagen and other basement membrane proteins round its cellular periphery. After transformation with a temperature-sensitive mutant of Rous sarcoma virus (tsRSV) the cells fail to deposit an extracellular matrix at the permissive temperature (35 degrees C), but retain the capacity to do so at the non-permissive temperature (41 degrees C). The synthesis of type-IV collagen is not affected by the temperature shift. Rama 712 cells fail to form tumours in syngeneic rats. However, Rama 712-tsRSV cells form tumours that are locally invasive but fail to metastasize. In histological sections, the tumour cells stain with an antibody to type-IV collagen, but do not deposit any extracellular type-IV collagen. Cells isolated from the tumours (Rama 712T) remain temperature-sensitive for the extracellular deposition of type-IV collagen when grown in vitro. Rama 712, Rama 712-tsRSV and Rama 712T fail to produce any detectable type-I or type-IV collagenase at either 35 degrees C or 41 degrees C. These results show that in this system extracellular deposits of basement membrane proteins are lost from invasive tumours produced by myoepithelial-type cells by mechanisms other than those due to the production of collagenolytic enzymes.
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PMID:Loss of basement membrane deposits and development of invasive potential by virally-transformed rat mammary cells are independent of collagenase production. 303 59


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