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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the clinicopathological classification of distinct stages of tumor progression in the melanocytic system, we have investigated the in vitro growth patterns and requirements of normal melanocytes and melanocytes isolated from different lesions of melanoma progression. Normal melanocytes depend on a combination of insulin-like growth factor (IGF-I) or insulin, 12-O-tetradecanoyl phorbol-13-acetate (TPA), alpha-melanocyte stimulating hormone (alpha-MSH), and basic fibroblast growth factor (bFGF) for in vitro proliferation. Nevus cells display a reduced need for TPA and are largely independent of bFGF. Both melanocytes and nevus cells have a finite lifespan in vitro and show no spontaneous transformation, whereas melanoma cells can be grown indefinitely in vitro. Cells from primary melanomas require only IGF-I or insulin for continuous growth, and metastatic melanoma cells can proliferate in base medium without addition of any growth factors or proteins. This progressive growth autonomy is paralleled by an increased competence for endogenous growth factor production. Among these growth factors, bFGF and melanoma growth-stimulatory activity (MGSA) act in an autocrine fashion. Melanoma-derived growth factors without apparent autocrine function, such as platelet-derived growth factor A and B (PDGF-A and PDGF-B) and transforming growth factor-alpha (TGF-alpha), might still be important for melanoma growth by stimulating surrounding normal fibroblasts, endothelial cells, or keratinocytes to secrete growth-promoting factors. The significance of growth factors such as transforming growth factor-beta (TGF-beta) and melanoma-inhibiting activity II (MIA II), which have a potentially negative autocrine function, remains unknown. The successful propagation of melanocytic cells of all stages of melanoma progression has yielded valuable insight into the mechanisms of growth regulation and malignant transformation.
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PMID:In vitro growth patterns of normal human melanocytes and melanocytes from different stages of melanoma progression. 144 12

Human esophageal and gastric carcinomas express multi-autocrine growth factors and hormones including epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and beta, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and sex hormones. Overexpression of EGF, TGF-alpha and EGF receptor (EGFR) by tumor cells is closely correlated with the tumor invasion and patient prognosis. This is substantiated by the facts that EGF and TGF-alpha act as autocrine growth factors and then induce the expression of mRNAs for multi-growth factors and their receptors (EGF, TGF-alpha, EGFR, ERBB2, PDGF). Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF-alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis. On the other hand, multiple oncogene alterations take place in the process of tumor progression. HST-1 and INT-2 genes which is a member of fibroblast growth factor gene family, are amplified in approximately 50% of primary tumors and all the metastatic tumors of esophageal carcinomas. The amplification of ERBB2 gene in metastatic gastric carcinomas is detected more frequently than in primary carcinomas. Overexpression of multi-growth factor-receptor systems might lead to genetical alterations. Scirrhous gastric carcinoma has vast fibrous stroma with rapid and extensive growth and exhibits high malignancy. Its fibrous stroma may account for synchronous overexpression of EGF, TGF-alpha, PDGF, IGF and TGF-beta by tumor cells. Most of well differentiated adenocarcinomas show overexpression of p 185ERBB2 and coexpression of p 185ERBB2, and EGFR evidently correlates with high malignancy. In conclusion, the accumulation and interaction of several growth factors produced by tumor cells are necessary for the progression of human esophageal and gastric carcinomas. They may be attributed to genetic changes including activation of oncogenes, inactivation and deletion of anti-oncogenes and transcriptional regulatory sequences.
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PMID:Growth factors in progression of human esophageal and gastric carcinomas. 209 74

Monoclonal antibodies (MAbs) to the human epidermal growth factor (EGF) receptor, the type I insulin-like growth factor (IGF) receptor, and the nerve growth factor (NGF) receptor were used to study the growth regulation of malignant cells. Anti-EGF receptor MAb 425 inhibited the growth of A 431 squamous carcinoma cells which express high numbers of EGF receptors on their surfaces. Growth inhibition induced by MAb 425 was accompanied by alterations of the cell-cycle distribution of these cells, indicating the ability of a monoclonal antibody to act as a biologically active ligand. Growth stimulation of melanoma cells by EGF was unrelated to EGF receptor expression on the cell surface. Insulin- and IGF-I-induced growth stimulation of melanoma cells was inhibited by MAb alpha IR-3 which reacts with the type I IGF receptor. This result indicates that the type I IGF receptor mediated growth stimulation not only by IGF-I but also by insulin. Normal melanocytes and cells of all stages of tumor progression expressed in tissue culture the receptor for NGF, but no effect on the growth of these cells has been observed.
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PMID:Interactions between growth factor receptors and corresponding monoclonal antibodies in human tumors. 283 Dec 41

The physiological role of insulin-like growth factor (IGF) II (IGF-II) in adult humans is poorly understood. Rather high levels of IGF-II persist in adult human serum, whereas, in rodents, IGF-II levels are very low. To investigate the physiological and carcinogenic effects of persistently elevated IGF-II in adults, we have produced two lines of transgenic mice in which high levels of IGF-II (20- or 30-fold increase above normal) are persistently maintained in the blood. The transgene is driven by the major urinary protein promoter, and it is highly expressed in the liver and perputial glands in both lines. The adult transgenic mice are smaller than controls, and their body composition is altered. Their lean body mass is reduced by 5-8%, whereas fat mass is reduced between 44 and 77%. The mice expressing the highest level of IGF-II (30x) develop hypoglycemia and hypoinsulinemia and IGF-I levels are normal. Mice in the lower expression line (20-fold elevated IGF-II) develop hypoglycemia progressively over their lifetime. Mice from both lines also develop a diverse spectrum of tumors at a higher frequency than controls after 18 months of age, and the most frequent types of tumors are hepatocellular carcinomas and lymphomas. Squamous cell carcinoma, sarcoma, and thyroid carcinomas also occurred in our test group. The long latent period before tumors arise and the wide spectrum of tumor types suggest that IGF-II may function primarily as a tumor progression factor in mice via autocrine and endocrine mechanisms of action.
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PMID:Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. 751 93

Several lines of evidence suggest that the growth factor insulin-like growth factor-II (IGF-II) is involved in the genesis of several types of tumors and may have autocrine effects on tumor progression when overexpressed. The human IGF-II gene is a complex transcription unit. Multiple transcripts are synthesized as a result of alternate promoter usage and the splicing of unique 5'-untranslated regions to common coding exons. We have examined two human tumor cell lines that both produce IGF-II protein which can function as an autocrine growth factor. Interestingly, each cell line uses a different IGF-II promoter; Hep3B cells predominantly activate P3, whereas in SW613 cells P4 is the preferred promoter. Here, we examine the differential transcriptional activation of the human IGF-II gene in Hep3B and SW613 cells by means of transient transfection assays and electrophoretic mobility shift analysis. The results indicate that production of IGF-II protein is mainly regulated at the level of transcription. Additional regulation takes place at the levels of messenger RNA stability and efficiency of translation.
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PMID:Differential promoter activation in two human insulin-like growth factor-II-producing tumor cell lines. 838 97

Retinoids are potent inhibitors of growth and tumor progression in many mammary carcinoma cell lines, though regulation of growth in nontumorigenic mammary epithelial cells by retinoids is less clear. Here, we have characterized the inhibition of MAC-T (a nontransformed bovine mammary epithelial cell line) cellular proliferation by retinoids and their role in regulating insulin-like growth factor binding proteins (IGFBPs). Retinoic acid (RA) (100 nM) was a potent inhibitor of MAC-T cell proliferation. Retinol was 10-100 times less effective. Neither retinoid could completely arrest growth at noncytotoxic concentrations. Retinoic acid inhibited cellular proliferation by 1 h (P < .05), but inhibition was fivefold greater by 24 h (P < .01). This second stage of growth inhibition (after 12 h) was dependent upon protein synthesis. However, RA-induced inhibition of cellular proliferation did not persist, with thymidine incorporation increasing toward control levels by 4 days in culture. Retinoic acid was less effective in inhibiting thymidine incorporation when cells were stimulated with insulin, des(1-3) IGF-I, or Long(R3) IGF-I when compared to cells stimulated with native IGF-I or serum. Inhibition of proliferation by RA was associated with increased levels of IGFBP-2 in conditioned media and in plasma membrane preparations. Treatment with insulin or des(1-3) IGF-I resulted in the appearance of IGFBP-3 in conditioned media and on the cell surface. However, RA significantly reduced IGFBP-3 levels in conditioned media and eliminated IGFBP-3 associated with the plasma membrane. Thus, RA is a potent but transient inhibitor of bovine mammary epithelial cell proliferation, and this growth inhibition is correlated with increased IGFBP-2 accumulation and inhibition of IGF-I stimulated IGFBP-3 protein secretion.
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PMID:Inhibition of cellular proliferation and modulation of insulin-like growth factor binding proteins by retinoids in a bovine mammary epithelial cell line. 865 3

Loss of imprinting (LOI) has been implicated in the pathogenesis of embryonal malignancies as well as adult cancers. Insulin-like growth factor II (IGF2) gene is an imprinted gene, normally transcribed only from the paternal allele. We investigated allele-specific expression of the IGF2 gene in 22 cases of renal cell carcinoma (RCC), a common adult-onset renal tumor. Sixteen cases (72%) were informative for IGF2 gene expression, and 9 (56%) of these cases showed biallelic expression of the IGF2 gene. Additionally, in four cases with biallelic expression from which uninvolved kidney tissue was available, LOI of the IGF2 gene was also demonstrated in the normal tissue. All cases with LOI of IGF2 were low-grade and low-stage tumors. LOI of the IGF2 gene in RCC was not associated with overexpression of IGF2 mRNA, whereas IGF2 overexpression was frequently observed in high-stage tumors. These results suggest that LOI of IGF2 predisposes to low-grade and low-stage tumors, whereas IGF2 overexpression may have a role in RCC tumor progression.
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PMID:Loss of imprinting of the insulin-like growth factor II gene in renal cell carcinoma. 920 56

To elucidate the physiological role of human stromelysin-3 (hST-3) in tumor progression and/or wound healing, insulin-like growth factor-binding protein-1 (IGFBP-1) was analyzed as a potential physiological substrate. hST-3 proteolysis generates two fragments of 16 and 9 kDa that react with IGFBP-1 monoclonal antibody, although they do not bind insulin-like growth factor-I (IGF-I) in ligand blot. N-terminal sequencing shows that hST-3 cleaves IGFBP-1 at the His140-Val141 bond located in the IGFBP-1 midregion. We show that IGFBP-1 inhibits IGF-I-induced survival and proliferation of BAF/3 cells, as well as IGF-I-mediated activation of phosphatidylinositol 3-kinase (PI 3-K). Co-incubation of the IGF-I. IGFBP-1 complex with hST-3 restores IGF-I-induced proliferation and PI 3-K kinase activity in these cells. BAF/3 proliferation is significantly increased with the hST-3-treated IGF-I.IGFBP-1 complex compared with that obtained using IGF-I alone. To produce this enhanced proliferation, IGF-I must bind to IGFBP-1 before hST-3 proteolysis, demonstrated using an IGF-I variant that does not bind IGFBP. IGFBP-1 also inhibits IGF-I-induced proliferation of the MCF-7 breast adenocarcinoma, and this inhibition was not seen in hST-3-transfected MCF-7 cells. Such proteolysis may thus play a role in in vivo tumor progression. These results indicate that hST-3 may regulate IGF-I bioavailability by proteolyzing IGFBP, thus favoring cell survival and proliferation.
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PMID:Identification of insulin-like growth factor-binding protein-1 as a potential physiological substrate for human stromelysin-3. 932 95

Expression of insulin-like growth factor-2 (IGF-2) has been reported in tissue specimens and cell lines of human colorectal cancers. However, the effects of IGF-2 in colorectal cancer patients are not well known. In this study, IGF-2 staining was performed on tissue samples from 92 patients with colorectal cancer, and the relationship of IGF-2 staining to clinicopathological variables, proliferating cell nuclear antigen (PCNA) staining and patient survival was analyzed. IGF-2 staining was correlated with tumor progression, PCNA staining and patient survival. Our results suggest that IGF-2 plays an important role in tumor progression and that IGF-2 staining is useful as a prognostic factor in colorectal cancer patients.
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PMID:Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival. 956 57

Various growth factors and basement membrane proteins have been implicated in the pathobiology of astrocytomas. The goal of this study was to determine the relative contribution of these two factors in modulating the phenotype of U-373 MG glioblastoma cells as determined by the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, and nestin. For these determinations, cells plated in serum-free medium were treated either with growth factors binding to tyrosine kinase receptors including transforming growth factor-alpha, epidermal growth factor, platelet-derived growth factor-AA, basic fibroblast growth factor, and insulin-like growth factor-1 or with basement membrane proteins including collagen IV, laminin, and fibronectin. The changes in the expression levels of intermediate filament proteins in response to these treatments were analyzed by quantitation of immunoblots. The results demonstrate that collagen IV and growth factors binding to tyrosine kinase receptors decrease the glial fibrillary acidic protein content of U-373 MG cells. Growth factors binding to tyrosine kinase receptors also decrease the vimentin content of these cells but do not affect their nestin content. On the other hand, basement membrane proteins decrease the nestin content of U-373 MG cells but do not affect their vimentin content. The significance of these results with respect to the role played by different factors in modulating the phenotype of neoplastic astrocytes during tumor progression is discussed.
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PMID:Effects of growth factors and basement membrane proteins on the phenotype of U-373 MG glioblastoma cells as determined by the expression of intermediate filament proteins. 977 47


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