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

With the use of the rat 13762 mammary adenocarcinoma tumor, an animal model for spontaneous mammary tumor metastasis was developed. The parental tumor implanted sc into the mammary fat pads of female Fischer 344 rats metastasized at low frequency to lymph nodes and lung and did not metastasize to other organs. Oophorectomy did not modify the metastatic properties of the parental 13762 tumor. Cell lines were adapted to tissue culture from lymph node or lung metastases, and these were compared to parental tumor transplants in spontaneous metastasis assays. Only the cell lines established from metastases were spontaneously metastatic within 23 days after sc implantation, indicating that tumor cell populations from metastases are more metastatic than are cells from the parental tumor. Several individual parental tumor-derived and lung metastasis-derived clones were compared for spontaneous metastatic potentials, cell culture morphologies, histologic structures at primary implant and secondary metastatic sites, and growth characteristics in vivo and in vitro. There was no correlation between any of these tumor and cellular properties and metastatic potential. The parental mammary tumor-derived, lymph node metastasis-derived, and lung metastasis-derived cell lines and clones with differing spontaneous metastatic properties should prove useful in studies on the roles of tumor cell and host properties in lymphatic and blood-borne metastasis.
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PMID:Development and biologic properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma. 695 Jan 80

Mammary neoplasms in yellow (C3H x VY-A vy) F-1 virgin female mice with the murine mammary tumor virus were distributed equally between the left and right sides. The ratio of thoracic to inguinal gland involvement was 6.4 to 3.6 indicating that the A vy mutation, which enhances age-specific mammary tumor incidence, apparently does not affect the distribution of mammary tumors. The average tumor size was similar in all mammary glands. Multiple tumors occurred seven times more frequently in the thoracic than in the inguinal glands. Metastases occurred more frequently in moribund mice than in those killed at a scheduled time, and the incidence of pulmonary metastases in both groups was associated with the duration of the mammary tumors, their size, their location, and the number of neoplasms. Adenocarcinomas in the thoracic glands metastasized to the lungs more frequently than those in the inguinal glands.
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PMID:Distribution of mammary gland neoplasms and factors influencing metastases in hybrid mice. 707 83

The frequency with which metastasis occurs for three tumor sublines derived from a single mouse mammary tumor, all of which grow preferentially in mammary fatpads (as compared to the subcutis), was determined from primary tumors growing in mammary fatpads and from primary tumors growing in the subcutis. A relatively metastatic subline was found to metastasize more readily from the mammary fatpad than from subcutaneous sites. The number of metastatic nodules found in the lungs of animals following surgical removal of primary tumors transplanted into intact mammary fatpads was significantly greater than the number of nodules in the lungs of animals following surgical removal of primary tumors transplanted subcutaneously. Two sublines, which do not readily metastasize from tumors growing subcutaneously, did not metastasize from tumors growing in mammary fatpads.
Invasion Metastasis 1981
PMID:Comparison of metastasis of mammary tumors growing in the mammary fatpad versus the subcutis. 718 87

The Fab fragments of antibodies against cell-type-specific surface antigens of mouse mammary epithelial cells (MME-antigens) were used to localize mammary tumors successfully. The radioiodine-labeled anti-MME (Fab) was injected into mice carrying simulated mammary metastases, and after 24 hours the amount of label per gram of excised tissue was several times greater in the tumor than in liver, brain, lung, or muscle. Kidney showed considerable accumulation of label but this appeared to be nonspecific. Kinetic studies revealed a rapid elimination of labeled Fab in the urine with only 1% of the injected dose remaining in the entire blood pool after 24 hours. Wit a high-purity germanium camera, mammary tumors were clearly located ty the 131I-labeled anti-MME (Fab), and normalization to 99mTc-pertechnetate distribution in the animal increased the specificity. The density of 131I-label was fourfold greater over the mammary tumor than over comparable areas of the mouse. No accumulation of 131I-anti-MME (Fab) was observed in nonmammary tumors nor in mammary tumors when labeled nonspecific Fab was used. An analogous system using an antihuman mammary epithelial antiserum is being developed for localization of breast metastases in humans.
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PMID:Localization of mammary tumors in vivo with 131I-labeled Fab fragments of antibodies against mouse mammary epithelial (MME) antigens. 728 75

Six examples of a breast neoplasm distinguished by gross and microscopic circumscription and prominent intracellular and intraacinar mucin are presented. These neoplasms are analogous to similar tumors which, although rare, more characteristically occur in the breasts of children. They apparently are slow-growing lesions and none manifested either local recurrence or metastases.
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PMID:Secretory carcinoma of the breast in adults. 743 74

Transgenic mice expressing the polyomavirus (PyV) middle T oncogene in the mammary epithelium develop multifocal mammary tumors that metastasize with high frequency. The potent transforming activity of PyV middle T antigen can, in part, be attributed to its ability to associate with and to activate a number of c-Src family tyrosine kinases (c-Src, c-Yes, and Fyn). As a first step toward assessing the role of individual c-Src family tyrosine kinases in PyV middle T antigen-induced mammary tumorigenesis, we have crossed transgenic mice carrying the mouse mammary tumor virus (MMTV)/PyV middle T antigen fusion gene with mice bearing a disrupted c-src proto-oncogene. In contrast to the rapid tumor progression seen in the original MMTV/PyV middle T antigen strains, mice expressing the transgene in the absence of functional c-Src rarely developed mammary tumors. After long latency, these mice did eventually develop abnormal hyperplastic mammary tissue. This growth disturbance was correlated with elevated expression of the PyV middle T antigen and the activation of the PyV middle T antigen-associated c-Yes tyrosine kinase. However, transgenic mice expressing the PyV middle T antigen in the mammary epithelium of wild-type or Yes-deficient mice developed multifocal mammary tumors with comparable kinetics. Taken together, these findings suggest that c-Src tyrosine kinase activity is required for PyV middle T antigen-induced mammary tumorigenesis and also illustrate an in vivo genetic approach to the dissection of mitogenic signal transduction pathways.
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PMID:Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. 750 74

In the present study we tested whether T cells retargeted with a bispecific antibody (bsAb) could block the growth of lung metastases of syngeneic mammary adenocarcinoma in immunocompetent mice. BALB/c mice were injected i.v. with tumor and i.p. with a genetically engineered bispecific F(ab')2 [bs(Fab')2] having specificity for murine CD3 epsilon chain and for the gp52 mouse mammary tumor viral glycoprotein, which is expressed on the tumor cells. The bs(Fab')2 was physically stable in blood and serum, was removed from the body with a half-time of 12-15 h, and accumulated in lymphoid tissue where it bound to T cells. We show that treatment of tumor bearing mice with the bs(Fab')2 significantly prolonged their survival relative to untreated controls. Two other genetically engineered bs(Fab')2s having specificity for murine CD3 epsilon chain and irrelevant antigens did not inhibit tumor growth. In addition, survival was not affected by bsAb therapy using a variant tumor cell line that expressed low levels of the gp52 target antigen. Inhibition of tumor growth was even more evident by histologic analysis. Treatment with the relevant bs(Fab')2 resulted in a marked reduction of tumor burden in lung sections taken on days 7, 9 and 11. This is the first report demonstrating that a bsAb can inhibit the growth of syngeneic solid tumor metastases in mice without addition of T cell activators.
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PMID:A bispecific antibody prolongs survival in mice bearing lung metastases of syngeneic mammary adenocarcinoma. 757 3

A conditional expression system was established whereby the human K-ras, v-src, and v-mos genes were cloned into a conditional expression vector downstream of the dexamethasone-inducible mouse mammary tumor virus long terminal repeat. Rat-1 fibroblasts were transfected with these constructs and selected in medium containing G418. Cloned transfectants were isolated and characterized for absolute dependence on dexamethasone for expression of oncogene products and anchorage-independent growth in soft agar. Expression of activated p21K-ras(val12) enabled the fibroblasts to degrade extracellular matrix collagen secreted by murine microvessel endothelial cells. Concurrent with p21K-ras(val12) induction a proteinase with the characteristic size and substrate specificity of transin, the murine homologue of the human matrix metalloproteinase stromelysin, was expressed and secreted. Induction of v-mos and v-src oncogenes resulted in little or no detectable transin expression respectively coinciding with a relative or absolute failure to increase degradation of extracellular matrix collagen. This study suggests that in this system the expression of the ras oncogene can contribute to the in vitro invasive behavior of tumor cells by upregulating the production of a metalloproteinase capable of degrading collagen synthesized by vascular endothelial cells.
Clin Exp Metastasis 1995 Jul
PMID:Degradation of endothelial cell matrix collagen is correlated with induction of stromelysin by an activated ras oncogene. 760 86

Most tumors grow progressively and overwhelm the host. The rare but documented cases of spontaneous regression of primary tumors are indicative of the potential of tumor-bearing hosts to develop a significant antitumor response. Because most tumors grow progressively in the host, it is not surprising that the majority of studies have focused on T lymphocytes that infiltrate these tumors. Although these studies have generated significant and useful information during the period of tumor growth, they can only speculate on the mechanisms that are involved in tumor rejection. We have used a well developed sponge model of concomitant tumor immunity that allows us to compare the immunologic events that occur during tumor progression vs rejection. In this model, an animal harboring a primary EMT6 mammary tumor is challenged with a secondary tumor implant through a pre-implanted gelatin sponge. During the manifestation of concomitant tumor immunity, the secondary tumor is rejected and the effector cells mediating the response are retained within the sponge matrix. Using this model we analyzed the TCR usage, cytotoxic activity of lymphocytes, and cytokine production at both tumor sites. The data revealed that tumor-rejecting lymphocytes isolated from the site of secondary tumor implant were cytotoxic toward EMT6 cells, whereas tumor-infiltrating lymphocytes isolated from the progressing primary tumor were not. Interestingly, the TCR-V beta repertoire of the tumor-infiltrating lymphocytes and tumor-rejecting lymphocytes were identical with V beta 1 and V beta 8 being predominant at both sites. Furthermore, the rejection site showed higher gene expression of IFN-gamma, TNF-alpha, and IL-10 whereas TGF-beta expression was slightly higher in the progressing tumors. These findings suggest that the disparate effector functions observed during tumor progression vs rejection are not caused by different T cell phenotypes but may be due instead to influences exerted by cytokines produced at the tumor sites.
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PMID:T lymphocytes infiltrating sites of tumor rejection and progression display identical V beta usage but different cytotoxic activities. 770 35

We have postulated that murine mammary tumor progression is fueled, in part, by tumor-associated macrophages that deliver sub-lethal oxidative stress to tumor cells. In the present study, we determined whether oxidative stress would affect murine mammary tumor cell attachment to laminin and fibronectin, critical functions in the metastatic process. Sublethal oxidative stress generated by exposure of cells to hydrogen peroxide (H2O2, 1-1000 microM/L) inhibited tumor cell attachment to immobilized laminin or fibronectin. This oxidant effect was blocked in the presence of catalase which removes H2O2. The inhibitory effect on attachment was rapid, with significant inhibition occurring at 5 min; total inhibition was achieved at 60 min with 1 mM H2O2. The oxidative stress effect was partially reversible at 20 h post-treatment and occurred at concentrations of H2O2 that do not adversely affect cell viability or growth. Pretreatment of tumor cells with H2O2 or hypoxanthanine and xanthine oxidase (to generate superoxide radical and H2O2) prior to intravenous injection, enhanced experimental lung tumor colony formation. The enhancement of experimental metastatic potential with enzyme-generated oxidative stress was completely reversed by catalase; the H2O2-mediated enhancement was only partially reversed with catalase. Thus, treatments that inhibit tumor cell attachment to extracellular matrix proteins in vitro enhance experimental metastasis in vivo.
Clin Exp Metastasis 1995 Jan
PMID:Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma. 782 Sep 52


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