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

A number of human cancer cell lines have been described as being invasive and metastatic in immune incompetent animals. However, it is difficult to assess metastatic spread of a subcutaneously injected or inoculated cell line, since an exact detection of all microfoci of human tumour cells in the animals by usual histological procedures would require extensive sectioning of the whole animal. To overcome this problem, we transduced human breast cancer cells with a replication-defective Moloney murine leukaemia retroviral vector (M-MuLV) containing both neoR (neomycin resistance) and lacZ genes. The resulting cell lines were selected for antibiotic (G418) resistance, and cell-sorted for lacZ expression. lacZ continued to be expressed in cultured cells for at least 20 passages without further G418 selection. The lacZ gene codes for beta-D-galactosidase, and cells expressing this gene stain blue with the chromogenic substrate X-gal. The lacZ-expressing cells retained the pre-transduction ability to traverse Matrigel in vitro, to form subcutaneous tumours in nude mice, and to grow invasively with the formation of metastases. X-gal staining showed high specificity, staining the tumour cells but not the surrounding mouse tissue on either whole tissue blocks or histological sections. The staining procedure was highly sensitive, allowing detection of microfoci of human cancer cells, and quantitative estimation of the metastatic capacity of the cells. These results indicate that lacZ transduction of human tumour cells is a powerful means of studying human cancer cell invasion and metastases in vivo.
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PMID:lacZ transduced human breast cancer xenografts as an in vivo model for the study of invasion and metastasis. 138 7

Retroviral-mediated gene transfer was employed to introduce an IL-1 alpha cDNA into an IL-6-dependent murine B-cell line. Bone marrow metastases and bone lesions were frequently observed following intravenous injection of these B cells into syngeneic mice. Because the retroviral vector also contained the neomycin phosphotransferase gene, metastatic cells could be easily recovered from bone marrow by addition of G418 to the culture medium. Interestingly, the metastatic B cells were found to retain their IL-6 dependency through several transplant generations. By comparison, intravenous injection of autonomously-growing B-cell lines generated in vitro by retroviral introduction of an IL-6 cDNA rarely resulted in bone marrow metastases. These results demonstrate that abrogation of growth factor dependency is neither necessary nor sufficient for the in vivo growth and dissemination of tumor cells in this experimental system. It is proposed that the increased metastasis of the IL-1 alpha-producing B-cells to bone marrow is due to alterations in cell adhesion molecules. The B-cell bone marrow metastasis model described here may be useful for studies of bone marrow homing and for evaluation of therapeutic regimens for multiple myeloma.
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PMID:Expression of retrovirally transduced IL-1 alpha in IL-6-dependent B cells: a murine model of aggressive multiple myeloma. 177 41

Recent work on molecular and genetic aspects of metastasis has emphasized the need for assays in immune-deficient animal hosts. The commonly used assays in athymic nude mice may not always be appropriate, and assays in other hosts are required. We have developed a metastasis assay in the naturally immune-deficient chicken embryo. As part of our characterization of this assay we have examined the clonality of individual experimental (i.v.-derived) metastases in this host. For these studies we developed a cell line, B16-Neo, from parental B16F1 murine melanoma cells. B16-Neo cells carry a stable drug-resistance marker, the bacterial neo gene, which confers resistance to the drug G418, but are unaltered in experimental metastatic properties in the chick embryo relative to parental B16F1 cells. We observe that the majority of individual liver tumors that arise following i.v. injection of mixtures of these cells contain cells of a single marker phenotype and are likely to be clonal in origin. These results are similar to those obtained by others for metastases in immune-competent mice, suggesting similar mechanisms of metastasis formation in these two systems. In both hosts it should be noted, however, that a small but significant proportion of metastases appear not to be clonal in origin.
Clin Exp Metastasis
PMID:Use of NeoR B16F1 murine melanoma cells to assess clonality of experimental metastases in the immune-deficient chick embryo. 316 9

Two low metastatic clones, NL-14 and NL-44, had been isolated from the murine colon 26 adenocarcinoma after in vivo selection and subsequent in vitro cloning. NL-14 is defective in the ability to induce platelet aggregation, but it has good in vivo growth potential. NL-44 possesses low growth potential after s.c. inoculation, but it has strong platelet-aggregating ability. A ouabain-resistant variant of NL-14 and a G418-resistant variant of NL-44 were established. Each resistant cell line conserved the phenotypes of platelet-aggregating ability or in vivo growth potential as compared to the respective parental cell line. These two clones were fused to examine the metastatic potential of hybridomas. Of eight hybridomas tested, six possessed both platelet-aggregating ability and good in vivo growth potential. These six hybridomas formed a higher number of pulmonary metastases after i.v. inoculation than the parental cells. Of the two low metastatic hybridomas, one was lacking in the ability to induce platelet aggregation, and the other showed the least potential for in vivo growth. Hybridoma clones with high platelet-aggregating activity in vitro were generally arrested well in the lung following i.v. inoculation. These results suggest that platelet-aggregating ability and in vivo growth potential are two major determinants for successful experimental lung metastasis of the colon 26 adenocarcinoma.
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PMID:Acquisition of metastatic ability in hybridomas between two low metastatic clones of murine colon adenocarcinoma 26 defective in either platelet-aggregating activity or in vivo growth potential. 360 71

Transfer of cytokine genes into tumor cells has proven a valuable approach for cancer treatment. In order to generate a more effective cancer vaccine, we transfected the human interleukin-6 (IL-6) gene into B16 melanoma cells. A B16 cell clone secreting the highest level of IL-6 was obtained by G418-resistant selection, limiting dilution and IL-6 assay. The IL-6-gene-transfected tumor cells exhibited in vitro growth inhibition, reduced tumorigenicity and decreased metastatic competence. After immunization with the inactivated IL-6-gene-transfected vaccine, the murine cytotoxic T lymphocyte activity, natural killer activity and lymphokine-activated killer activity increased markedly. After treatment with the vaccine, the tumor-bearing mice showed significant growth inhibition of subcutaneous tumor, reduction in pulmonary metastases and extension of survival time. The above therapeutic effect was better when low-dose IL-2 was administered simultaneously, although this dosage of IL-2 had no in vivo antitumor effect. These data demonstrated that IL-6-gene-transfected cancer vaccine has a potent antitumor effect via efficient induction of antitumor immunity, and a better therapeutic effect could be achieved when the vaccine is combined with low-dose IL-2 as adjuvant.
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PMID:Induction of antitumor immunity and treatment of preestablished tumor by interleukin-6-gene-transfected melanoma cells combined with low-dose interleukin-2. 749 43

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

Mouse spleen cells transfected with pSV2 neo by CaPO4 precipitation were fused with highly metastatic cell clone (PLA801-D95) from human large cell lung cancer cell line. Hybrid cell clone PMS-2 was obtained after G418(400/ml)selection. After injection of 7 x 10(6) PMS-2 cells into nude mice, there was a tumor nodule developed, but the metastatic foci could not be found while 3 x 10(6) PLA801-D95 cells would metastasize to lung and lymph nodes after they were injected into nude mice. It might indicate that sometime mouse spleen cells could not suppress tumor formation but the metastatic potential could be suppressed by the fusion of mouse spleen cells with the lung cancer cells. The results of growth curve, serum independence and incorporation rates of H-thymidine all showed that the growth rates of parental cells were higher than those of PMS-2. Our data suggest that suppression of tumorigenicity and metastatic potential could be controlled by different kinds of genes, and the cloning of metastasis suppressor gene by subtractive hybridization is ongoing in our laboratory.
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PMID:[A primary observation on the effect of cell fusion on metastatic potential of tumor cells]. 870 58

A clonal cell line, 1-1ras1000, transformed by the activated c-Ha-ras oncogene, does not form metastases after i.v. injection into mice (experimental metastasis assay). Here, we show that this cell line is useful as a recipient to detect metastasis-inducing genes, using a transfection assay. Cells (1-1ras1000) were susceptible to metastasis induction by transfection with either v-src or genomic DNA from a v-src-and v-fos-transferred highly metastatic rat cell line (SR202). The susceptibility of 1-1ras1000 cells for lung metastasis induction was suitable for a genomic transfection assay to detect a metastasis-inducing gene in the transfected cells which had incorporated genomic DNA from donor metastatic tumor cells. When DNAs extracted from 7 human tumors were tested for metastasis induction, 2 DNAs from nonmalignant tumors (non-tumorigenic tumors in athymic nude mice) (2/2) were negative and 4 DNAs from malignant tumors (4/5) were positive in 1-1ras1000 cells for primary transfection. in one of the resulting metastases, the ability to metastasize was also transferred in the second and third cycles of genomic DNA transfection at high frequencies. All of the resulting metastases carried the human repetitive Alu sequence. Neither re-arrangements of the endogenous c-Haras nor changes of protein amounts were detected. Recipient 1-1ras1000 cells had a negligible rate of spontaneously metastatic conversion during in vitro cultivation and transfection processes. The resulting metastasized cells were easily isolated from the lung after culturing in selection medium containing G418 (geneticin). Isolated cells stably retained the ability to form metastatic lung nodules when re-injected into mice. Thus, 1-1ras1000 cells appear to be a useful system for the isolation of metastasis-inducing genes from human metastatic tumors.
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PMID:A BALB/c 3T3-transformed cell line suitable for transfection assay of metastasis-inducing genes. 909 70

Overexpression of p185erbB2/neu has been detected in many adenocarcinomas, including prostatic cancer. In this study, a nontumorigenic cell line isolated from the rat prostatic epithelium (NbE) transfected with the activated oncogene p185neu-T was used to investigate the role of this oncogene in tumor progression. When clones overexpressing p185neu-T were injected orthotopically (1.5 to 2 x 10(6) cells) into the dorsal-lateral prostates of nude mice, prostatic tumors were detected in all mice injected and metastasis to the skeletal muscle in the rib area in 60-80% of the mice injected. Tumor and metastasis origin was confirmed by reselection with G418 and reverse transcriptase-polymerase chain reaction. Control cell lines produced no prostatic tumors or metastases. Incubation at low density (12500 cells/2 cm2) in serum-free medium revealed that clones overexpressing p185neu-T had a higher rate of [3H]thymidine incorporation than did control clones on 3, 5, and 7 d after plating (P < or = 0.0001) and constitutively overexpressed the 2.6-kb ornithine decarboxylase transcript. Additionally, clones overexpressing p185neu-T demonstrated an increased expression of epidermal growth factor receptor and p180erbB4, as judged by RNA blot analysis. Together these data support the hypothesis that overexpression of p185neu-T fosters tumor progression by several pathways, including induction of the metastatic cascade, increased proliferative capabilities, and increased expression of other members of the erbB2 gene family.
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PMID:Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE). 925 83

It is extremely rare for brain glioblastoma to metastasize extracranially. To elucidate whether glioblastoma cells remain non-metastatic when ectopically transplanted and CD44v gene is introduced, glioblastoma RG2-m cells were transfected with CD44v gene sequence encompassing v3-v10. After selection in culture medium with G418, CD44v expressing RG2-a cells were cloned. With RG2-a and its parental counterpart RG2-m, a series of experimental metastasis assays were performed in syngeneic F344 rats. When inoculated subcutaneously and in the foot-pad, both RG2-m and RG2-a cells metastasized spontaneously to the regional lymph nodes and lungs. However, metastasis of RG2-a was more severe and more organs were involved when compared to that of the parental RG2-m cells. The results indicate that glioblastoma becomes metastatic if extracranially transplanted and expression of CD44v would further enhance its metastatic patential.
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PMID:[Enhanced metastatic potential of rat RG2 glioblastoma cells transfected with CD44v (meta-1) sequence]. 938 71


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