Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P13232 (Interleukin-7)
 580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lectin-binding characteristics of a previously described highly metastatic variant (clone 4), derived in vivo from a poorly metastatic rat mammary adenocarcinoma (DMBA-8), have been investigated. of the lectins studied clone 4 cells, unlike the parent cells, bound Ulex europaeus agglutinin (UEA-1; specificity alpha-L-fucose) and peanut agglutinin (PNA; specificity D-galactose). These differences may be related to the greatly enhanced ability of clone 4 cells to form lung foci after intravenous injection. After neuraminidase treatment the differential binding of PNA, as shown by flow cytofluorography, was abrogated whereas that of UEA was unchanged. After separation by SDS-PAGE, four proteins in total cell extracts of clone 4 cells bound 125I-UEA applied to the gels. These had subunit molecular weights greater than 100,000 daltons and were also found in cellular extracts of another highly metastatic rat mammary adenocarcinoma (MAT 13762-B), but were missing from DMBA-8 cell extracts. In clone 4 and MAT 13762-B cells exogenous 3H-fucose was mainly incorporated into four fucoproteins of similar molecular weights to those which bound 125I-UEA. DMBA-8 cells, which incorporated slightly less exogenous fucose, showed a different pattern of fucoprotein labelling, which would seem to explain why DMBA-8 cells failed to bind UEA. Differences in cell surface protein iodination patterns were also noted between DMBA-8 and clone 4 cells.
Invasion Metastasis 1987
PMID:Lectin-binding characteristics of related high- and low-metastatic rat mammary adenocarcinoma cell lines. 367 43

The purpose of this investigation was to determine whether cells transformed by herpes simplex virus type 2 (HSV-2) can be stimulated to synthesize prostaglandins (PG). Stimulation was determined by measuring the release of PG into overlay fluids from cell monolayers prelabeled with [3H]arachidonic acid. Results showed that Ca2+ ionophore A-23187 markedly stimulated arachidonic acid release starting 30 min after treatment of HSV-2-transformed and nontransformed rat embryo fibroblast cells. However, only HSV-2-transformed cells were stimulated in production of PG. HSV-2-transformed, nontumorigenic, rat embryo fibroblast, line G, clone 2.0 cells synthesize nearly equal amounts of prostaglandin E2 (PGE2) and prostaglandin F2 alpha, while tumor (rat fibrosarcoma) cells synthesize primarily PGE2. Stimulation of PGE2 synthesis by Ca2+ ionophore A-23187 or 12-O-tetradecanoyl-phorbol-13-acetate decreased as rat fibrosarcoma cells were serially passaged in tissue culture. At low passage of parental rat fibrosarcoma cells, four distinct morphological clonal cell lines were isolated, which varied markedly in their capacity to be stimulated in PG synthesis by 12-O-tetradecanoyl-phorbol-13-acetate. There was correlation between the capacity of clone 1 cells to be stimulated in PGE2 synthesis by serum alone and capacity of the tumors produced by the clone 1 cells to metastasize to the lungs of syngeneic tumor-bearing rats. In summary, cell transformation by HSV-2 appears to be essential for stimulation of PG synthesis in cells. The capacity to be stimulated in arachidonic acid metabolism and PG synthesis may be important in the process of carcinogenesis by a putative human cancer virus.
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PMID:Calcium ionophore A-23187 and 12-O-tetradecanoyl-phorbol-13-acetate stimulation of prostaglandin synthesis in herpes simplex virus type 2-transformed rat cells. 632 82

In order to examine a role of carcinoembryonic antigen (CEA) in metastasis, cDNA encoding CEA was introduced into a clone of human colorectal carcinoma SW1222 cells. Western blot analysis revealed that all transfectants express CEA of 180 kDa while the parent clone does not. In the transfectants, the level of CEA expression in clone 3 was higher than that of clone 1. Clone 3 formed aggregates rapidly after suspended by trypsinization while clone 1 did not. In experimental metastasis assay where tumor cells were injected intrasplenically, clone 3 exhibited a higher liver-metastatic activity than clone 1. Fab fragment of anti-CEA antibody significantly inhibited both the cell aggregation and the liver metastases caused by clone 3. These findings suggested that CEA expressed on the cell surface may play an important role in hepatic metastasis from colorectal carcinoma, possibly through its cell adhesion activity.
Clin Exp Metastasis 1994 Jul
PMID:Metastatic potential of human colorectal carcinoma SW1222 cells transfected with cDNA encoding carcinoembryonic antigen. 803 6

The process of cancer metastasis consists of multiple sequential and highly selective steps. The vast majority of tumor cells that enter the circulation die rapidly and only a few survive and proliferate to form distant metastases. This survival is not random. Metastases are clonal in origin and are produced by specialized subpopulations of cells that preexist in a heterogeneous primary tumor. Metastatic cells of the murine K-1735 melanoma survive in the circulation to produce experimental lung metastases, whereas nonmetastatic cells do not. After incubation with different cytokines or LPS, nonmetastatic cells exhibit a high level of inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production, whereas metastatic cells do not. To provide direct evidence for the inverse correlation between the production of endogenous NO and the ability of K-1735 cells to produce metastasis in syngeneic mice, highly metastatic clone 4 cells (C4.P), which express low levels of iNOS, were transfected with a functional iNOS (C4.L8), inactive mutated iNOS (C4.S2), or neomycin resistance (C4.Neo) genes in medium containing 3 mM NMA. C4.P, C4.Neo3, and C4.S2.3 cells were highly metastatic, whereas C4.L8.5 cells were not. Moreover, C4.L8.5 cells produced slow-growing subcutaneous tumors in nude mice, whereas the other three cell lines produced fast-growing tumors. In vitro studies indicated that the expression of iNOS in C4.L8.5 cells was associated with apoptosis. Multiple intravenous injections of liposomes containing a synthetic lipopeptide upregulated iNOS expression in murine M5076 reticulum sarcoma cells growing as hepatic metastases. The induction of iNOS was associated with the complete regression of the lesions. Collectively, these data demonstrate that the expression of iNOS in tumor cells is associated with apoptosis, suppression of tumorigenicity, abrogation of metastasis, and regression of established hepatic metastases.
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PMID:Activation of nitric oxide synthase gene for inhibition of cancer metastasis. 869 Oct 63

The process of cancer metastasis consists of multiple sequential and highly selective steps. The vast majority of tumor cells that enter the circulation die rapidly; only a few survive to produce metastases. This survival is not random. Metastases are clonal in origin and are produced by specialized subpopulations of cells that preexist in a heterogeneous primary tumor. Experimental studies concluded that metastatic cells survive in the circulation whereas nonmetastatic cells do not. In part, this difference is due to an inverse correlation between expression of endogenous inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) and metastatic potential. Direct evidence for the role of iNOS in metastasis has been provided by our data on transfection of highly metastatic murine K-1735 clone 4 (C4.P) cells which express low levels of iNOS, with a functional iNOS (C4.L8), inactive mutated iNOS (C4.S2), or neomycin resistance (C4.Neo) genes in medium containing 3 mM of the specific iNOS inhibitor NG-L-methyl arginine (NMA). C4.P, C4.Neo, and C4.S2 cells were highly metastatic, whereas C4.L8 cells were not. Moreover, C4.L8 cells produced slow-growing subcutaneous tumors in nude mice, whereas the other 3 cell lines produced fast-growing tumors. In vitro studies indicated that the expression of iNOS in C4.L8.5 cells was associated with either cytostasis or cytolysis via apoptosis, depending upon NO output. The tumor cells producing high levels of NO underwent autocytolysis and produced cytolysis of bystander cells under both in vitro and in vivo conditions. Multiple i.v. injections of liposomes containing a synthetic lipopeptide upregulated iNOS expression in murine M5076 reticulum sarcoma cells growing as hepatic metastases. The induction of iNOS was associated with the complete regression of the lesions. Transfection of interferon-beta suppressed tumor formation and eradicated metastases, which was apparently linked to iNOS expression and NO production in host cells such as macrophage. Besides mediating cell death, NO produced tumor suppression by regulating expression of genes related to metastasis, e.g., survival, invasion, and angiogenesis. Suppression of metastasis can be achieved through use of immunomodulators that induce iNOS expression in tumor lesions or by the direct delivery of the iNOS gene to tumor cells or host cells through liposome and/or viral vectors.
Cancer Metastasis Rev 1998 Mar
PMID:Therapy of cancer metastasis by activation of the inducible nitric oxide synthase. 954 23

We have shown previously that the relative expression of a truncated oestrogen receptor-alpha variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-deleted and exon 7-deleted oestrogen receptor-alpha variant mRNAs in 15 primary breast tumour samples and in synchronous axillary lymph node metastases. Overall, there were no significant differences between the primary tumours and the matched metastases in the relative expression of these three specific variant mRNAs. Furthermore, the pattern of all deleted oestrogen receptor-alpha variant mRNAs appeared conserved between any primary and its matched secondary tumour.
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PMID:Oestrogen receptor-alpha variant mRNA expression in primary human breast tumours and matched lymph node metastases. 1007 Sep

A nonhydrolyzable ether analogue of RRR-alpha-tocopherol, 2,5,7,8-tetramethyl-2R-(4R, 8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid, called RRR-alpha-tocopheryloxyacetic acid or RRR-alpha-tocopherol ether-linked acetic acid analogue (alpha-TEA), exhibits antitumor activity in vitro and in vivo using a syngeneic BALB/c mouse mammary tumor model (line 66 clone 4 stably transfected with green fluorescent protein). Treatment of cells with 5, 10, and 20 micro g/ml alpha-TEA for 3 days produced 6, 34, and 50% apoptosis, respectively, and treatment of cells with 10 micro g/ml for 2, 3, 4, and 5 days produced 20, 35, 47, and 58% apoptosis, respectively. A liposomal formulation of alpha-TEA administered by aerosol reduced s.c. tumor growth and lung metastasis. Alpha-TEA-treated animals showed a significant decrease in tumor volumes over 17 days of aerosol treatment (P < 0.001). Forty percent of aerosol as well as untreated control mice had visible, macroscopic lung metastases versus none (0%) of the alpha-TEA-treated mice. On the basis of fluorescence microscopic examination of the surface (top and bottom) of flattened whole left lung lobes, an average of 60 +/- 15 and 102 +/- 17 versus 11 +/- 4 fluorescent microscopic metastases was observed in aerosol control and untreated control versus alpha-TEA-treated animals, respectively. Alpha-TEA formulated in ethanol + peanut oil (5 mg/mouse/day) delivered by gavage did not reduce s.c. primary tumor burden; however, fluorescent microscopic lung metastases were significantly reduced (P < 0.0021). In summary, alpha-TEA formulated in liposomes and delivered by aerosol is a potent antitumor agent and reduces lung metastasis.
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PMID:Novel vitamin E analogue decreases syngeneic mouse mammary tumor burden and reduces lung metastasis. 1274 5

Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression. Since increased expression of WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in metastatic cancer cells to sustain high endocytic activity, essential for promotion of oncogenic activation and cancer cell survival. Here, we have delineated the underlying molecular mechanism of WDFY1 synthesis by NRP2. Our results indicated that NRP2 inhibits WDFY1 transcription by preventing the nuclear localization of a transcription factor, Fetal ALZ50-reactive clone 1 (FAC1). Our finding is novel as transcriptional regulation of a gene by NRP2 axis has not been reported previously. Regulation of WDFY1 transcription by NRP2 axis is a critical event in maintaining metastatic phenotype in cancer cells. Thus, inhibiting NRP2 or hyper-activating WDFY1 can be an effective strategy to induce cell death in metastatic cancer.
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PMID:NRP2 transcriptionally regulates its downstream effector WDFY1. 2702 95