Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Work done in our laboratories, using a murine model, indicates that suppression of host immune responses might be due to secretion of soluble factors by tumor cells. The H238 cells (BALB/c embryonic fibroblasts transformed by UV-inactivated herpes simplex virus Type 2) exhibit progressive tumor growth with subsequent decrease in lymphoproliferation. To further study the suppressive effects of a tumor, H238 conditioned medium (CM) was tested for its ability to block murine and human mitogenic and allogeneic lymphocyte responses. PHA, Con A and LPS were used as mitogens. Lymphoproliferation, in the presence of increasing amounts of H238 CM, resulted in a greater degree of suppression of [3H]thymidine ([3H]Tdr) uptake, in both human and mouse systems. The kinetics of proliferation in the presence of concentrated H238 CM (cCM) showed that depression was evident regardless of the time of cCM addition, thereby affecting it at any stage of the cell cycle. Treatment of H238 cCM using acid (pH 2.3), base (pH 9.6), trypsin (100 micrograms/ml), heat (56 degrees C, 100 degrees C) and freeze-thawing, restored PHA-stimulated lymphoproliferation. Dialysis of H238 cCM showed that the molecular weight of the suppressor lies between 15 and 25 kDa. Northern blot analysis demonstrated the presence of a TGF-beta transcript in H238 cells. Neutralization of the H238 cCM with monoclonal antibody to TGF-beta resulted in complete abrogation of suppressive activity in spleen cell lymphoblastogenesis. These results suggest that TGF-beta appears to be the main inhibitor of immune responses found in this HSV-2-induced murine tumor cell line. Such tumor-induced modulations may contribute to the outcome of immunotherapy in the tumor-bearing host.
 ...
PMID:Suppression of immune responses by herpes virus type 2-transformed murine tumor cells. 166 30

The mouse C3H teratoma-derived cell line 1246 is an adipogenic cell line which stringently requires insulin to proliferate and differentiate in defined medium. From this cell line an insulin-independent cell line called 1246-3A was isolated. It was found that, in contrast to 1246 cells, 1246-3A cells had lost the ability to differentiate and became tumorigenic when injected at a density of 10(6) cells/mouse into syngeneic host C3H mice. In addition, they produce in their culture medium transforming growth factor alpha- and beta-like polypeptides which stimulate their proliferation. Highly tumorigenic insulin-independent cell lines able to give rise to tumor when injected at a density of 10(4) cells/mouse were isolated by using an in vitro-in vivo shuttle technique. The highly tumorigenic cell lines have lost the response to TGF-beta 1. The binding of TGF-beta 1 to the nontumorigenic parent cell line or to cells displaying increased tumorigenic properties was investigated. The data presented here indicate that the increased tumorigenicity is accompanied by a progressive decrease of specific binding of TGF-beta 1 to the cells. However, the decreased number of cell surface TGF-beta 1 binding sites in the highly tumorigenic cells did not correlate with an increase in the secretion of TGF-beta protein by the tumorigenic cells, as all of TGF-beta produced by the cells was in a latent form. Affinity cross-linking experiments indicated that the 1246 cell line displayed several TGF-beta cross-linked molecular species (MW 140, 92, and 70 kDa). Increase of tumorigenicity was accompanied by a marked decrease in the intensity of the cross-linked bands, particularly of the 92 and 70 kDa species.
 ...
PMID:Decreased transforming growth factor-beta response and binding in insulin-independent teratoma-derived cell lines with increased tumorigenic properties. 166 Apr 84

The results summarized above suggest that assembly of fibronectin is a fundamental biological process and that knowledge of the process of assembly may reveal new ways by which cells interact with extracellular molecules. Deposition of a fibronectin matrix seems to be regulated as tightly as synthesis of fibronectin or expression of adhesion receptors for fibronectin and is influenced profoundly by two products of blood coagulation--TGF-beta released from platelets and factor XIII activated by thrombin. Fibronectin assembly may be important in all sorts of physiological and pathophysiological processes. Cell A--for instance, a stromal cell--can influence the behavior of cell B--for instance, a lymphocyte--by assembling fibronectin made by cell C--for instance, a hepatocyte. We hope that the testable models of assembly presented in this paper will lead to new understanding of the process of assembly and suggest new modalities for treatment of diseases that result in fibrosis, damaged tissues, and neoplastic growth.
 ...
PMID:Assembly of fibronectin into extracellular matrix. 167 33

The multidrug transporting cell membrane molecule P-glycoprotein can be spontaneously expressed in human glioma cells. Transcripts of mdr genes were detected in glial tumor cells by polymerase chain reaction and Northern blotting, expression of P-glycoprotein was analyzed by immunocytochemistry and functional activity by cytofluorometry of fluorescent probe transport. In vitro treatment of glioma cells with vincristine induced coordinate over-expression of both mdr1 and mdr3 genes associated with very high P-glycoprotein-mediated multidrug transport, resistant to the inhibitory activity of chemosensitizers like verapamil. The physiological modulators of multidrug transport are as yet unknown. We therefore initiated a screening program to analyze the effects of cytokines on multidrug transport. We observed, that transforming growth factors (TGF)-beta 1, -beta 2, and -beta 1.2-but not the related bone morphogenetic protein (BMP) 2--inhibited multidrug transport. Interestingly, BMP 2 antagonized the TGF-beta induced inhibition of multidrug transport.
 ...
PMID:Spontaneous multidrug transport in human glioma cells is regulated by transforming growth factors type beta. 167 77

alpha 2-Macroglobulin (alpha 2M) is known as an inhibitor of various proteinases and to bind several of the growth factors. We previously demonstrated that clonal variation exists in the production of alpha 2M in a human melanoma and that this variation may be associated with growth stimulation. We have now analyzed six human melanoma cell lines for the simultaneous expression of TGF-alpha, TGF-beta, PDGF-A chain, PDGF-B chain, and tumor-associated alpha 2M. In Northern blot analysis TGF-alpha was detected in four of the cell lines, TGF-beta in all, PDGF-A chain in three, and PDGF-B chain in none of the cell lines. alpha 2M, detected by immunoblotting, varied significantly between the different melanoma cell lines and only one cell line was found to be negative. Evaluation of growth-promoting activity in conditioned media suggested that alpha 2-macroglobulin, secreted by these tumor cell lines, is a significant modulator of melanoma cell growth.
 ...
PMID:Coexpression of tumor-associated alpha 2-macroglobulin and growth factors in human melanoma cell lines. 169 62

We investigated the expression of transforming growth factor beta 1 (TGF-beta 1) mRNA in tumor tissues surgically removed from ten patients with hepatocellular carcinoma (HCC). All HCC tissues expressed TGF-beta 1 mRNA at different levels, indicating the presence of activated transcription of TGF-beta 1 gene in human HCC tissues in vivo. The level of TGF-beta 1 mRNA expression showed no relationship to main tumor size of plasma alpha-fetoprotein level. Some HCC tissues presenting a relatively low grade of histological differentiation showed the highest levels of TGF-beta 1 mRNA expression.
 ...
PMID:Expression of transforming growth factor-beta 1 mRNA in human hepatocellular carcinoma. 170 20

The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.
 ...
PMID:TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis. 171 Apr 62

Human buccal epithelial cells have been reared from explants maintained in supplemented MCDB 153 medium. Primary epithelial outgrowths show typical structural features and uniformly express keratins; subunit analyses demonstrate expression of keratins 5, 6, 14, 16/17, and 19. The cells exhibit up to 6% colony forming efficiency and divide at about 0.8 population doublings per day on fibronectin/collagen-coated dishes at clonal density. Studies of markers of proliferation and differentiation in buccal epithelial cells indicate that epidermal growth factor, cholera toxin, retinoic acid, and pituitary extract each exhibit a distinctive ability to enhance growth and variably affect cell migration and cell surface area. Transforming growth factor beta-1 inhibits growth and increases surface area without affecting migration, involucrin expression, and cross-linked envelope formation. Moreover, exposure of cells to fetal bovine serum, the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate or an elevated Ca2+ concentration (from 0.1 to 1 mM) inhibits growth and induces squamous differentiation as indicated by inhibition of migration, increases in surface area, involucrin expression, or formation of cross-linked envelopes. The results show that epithelial cells can be reproducibly derived from explant cultures of human buccal mucosa specimens and the cells transferred under serum-free conditions. Buccal epithelial cells in culture undergo a pattern of growth and differentiation that mimics parakeratinization in vivo and variably respond to several agents shown to modulate growth of cells that originate from other types of epithelia.
 ...
PMID:Growth regulation of serum-free cultures of epithelial cells from normal human buccal mucosa. 171 53

An increasing number of polypeptide growth factors have been identified that regulate not only cell proliferation but also an extraordinary range of cell activities, including matrix protein deposition and resolution, the maintenance of cell viability, cell differentiation, inflammation, and tissue repair. Normal cells appear to require growth factors for proliferation and for maintenance of viability. Cells that secrete a polypeptide growth factor have an advantage in growth. These factors can act either externally through cell surface receptors or internally during the transport of receptors and growth factors through the endoplasmic reticulum and Golgi apparatus, causing autocrine stimulation of cell growth. Depending on the cell type, growth factors can also be potent inhibitors of cell growth rather than stimulators of growth, and the effect can depend on the presence or absence of growth factors. Among the growth factors considered, IGFs are unusual in that they function both as endocrine and as autocrine/paracrine agents. IGF-II, which is associated with fetal growth, is the IGF most frequently expressed by tumors. There is now convincing evidence that some tumors secrete sufficient IGF-II to have systemic endocrine effects as recognized as nonislet cell tumor hypoglycemia. PDGF is normally highly concentrated in platelets and has major significance in stimulation of cellular proliferation in inflammation and wound repair. Normally, this proliferation is self-limited, but the secretion of PDGF by tumors and its effects on cell proliferation of tumors persist. The fact that PDGF B monomer has an identical structure with that of the proto-oncogene C-cis further strengthens the connection between PDGF and tumor growth. EGF has a restricted role in normal physiology, but its close relative, TGF-alpha, is widely distributed in normal and neoplastic tissues. The common receptor for EGF and TGF-alpha is present in many normal and neoplastic cell types. The EGF receptor is the product of the C-erb gene. The oncogene V-cis is a truncated form of the EGF receptor whose tyrosine kinase activity is not dependent on ligand binding. TGF-beta exists in multiple forms. Although it can transform the morphology of certain cell lines in culture, it probably does not act generally as a mitogenic agent. Its major physiologic role in the body appears to be the stimulation of mesenchymal matrix formation. It is of special importance in the regulation of bone matrix formation. Its expression is increased in many tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Tumor secretion of growth factors. 171 47

Within human carcinomas, there is often an infiltration of lymphocytes and other cells of the immune system. A variety of cytokines are produced by such cells that could have a paracrine influence on the growth of tumor epithelium. The effect of one of these cytokines, interleukin-4 (IL-4), on human breast and colon cancer cell lines was therefore examined. IL-4 inhibited the growth of human colon (HT 29) and breast [MCF-7 wild type (MCF-7 WT), MCF-7 Adriamycin-resistant (MCF-7r), MDA-MB-231, and MDA-MB-468] carcinoma cells in culture. Competitive binding of 125I-IL-4 demonstrated the presence of 2000 high affinity IL-4-binding sites on HT 29 cells. The Kd for specific binding of 125I-IL-4 to HT 29 cells was 77 pM. Further studies were conducted on the estrogen-dependent MCF-7 WT and estrogen-independent MDA-MB-231 breast carcinoma lines. Concentrations of IL-4 of 10-100 nM were required to significantly inhibit growth of these carcinoma cell lines; e.g., with MCF-7 WT cells, half-maximal inhibition of growth occurred at 20 nM IL-4. Specific binding of 125I-IL-4 was detected to MCF-7 WT and MDA-MB-231 cells, but the low level of binding precluded Scatchard analysis. IL-4 inhibited 90% of the 17 beta-estradiol-stimulated growth of MCF-7 WT cells in a dose-dependent manner but without a change in estrogen receptor expression. Inhibition of growth by IL-4 was less in the absence of estrogens. Combined treatment with IL-4 and other known inhibitors of breast carcinoma cell growth [transforming growth factor-beta 1 (TGF-beta 1) and the antiestrogen tamoxifen] showed additive inhibition. The hormone-independent cell lines MCF-7r and MDA-MB-231 were additively inhibited by IL-4 and TGF-beta 1. This was not the case with MDA-MB-468 cells in which inhibition by IL-4 and TGF-beta 1 was of similar magnitude but no significantly greater effect was observed on combined treatment. No secretion of IL-4 was detected from these cell lines either basally or on treatment with TGF-beta 1 or tamoxifen, and we conclude that IL-4 is a nonautocrine inhibitor of breast carcinoma cell growth.
 ...
PMID:Inhibition of colon and breast carcinoma cell growth by interleukin-4. 172 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>