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

In this article we have reviewed and discussed the results of our investigation of lipid metabolites as modulators of epidermal growth factor (EGF) signaling pathways. We have studied epidermal growth factor-dependent mitogenesis in BALB/c 3T3 and Syrian hamster embryo (SHE) cells in culture. We observed that EGF stimulates the formation of prostaglandins in BALB/c 3T3 cells and their formation appears to be necessary for EGF dependent mitogenesis. EGF did not stimulate PGE2 formation in SHE cells and in fact, exogenously added PGE2 inhibited mitogenesis. In both cell lines, EGF stimulated the formation of lipoxygenase-derived 13(S)-hydroxyoctadecadienoic acid (13-HODE) and inhibition of 13-HODE formation attenuated mitogenesis. The addition of 13-(S)-HODE enhanced EGF-dependent mitogenesis but when added alone, the compound was not mitogenic. Other metabolites, including lipoxygenase metabolites of arachidonic acid, were either weak simulators of EGF-dependent mitogenesis or essentially inactive. The 13(S)-HODE appears to be formed by an apparently unique lipoxygenase that is regulated by the tyrosine kinase activity of the EGF receptor. The mechanisms by which lipids, particularly the lipoxygenase-derived linoleic acid metabolites, modulate the EGF signaling pathways leading to cell proliferation is discussed. The possible significance of lipoxygenase and prostaglandin H synthase-dependent metabolism of unsaturated fatty acids in breast and colon cancer is also discussed.
Cancer Metastasis Rev 1994 Dec
PMID:Cellular proliferation and lipid metabolism: importance of lipoxygenases in modulating epidermal growth factor-dependent mitogenesis. 771 98

Human colon cancer (Moser) cells produce and secrete epidermal growth factor (EGF) and respond to EGF via an autocrine/paracrine mode through the cell surface EGF receptor (EGFR). In this report we show that EGF promotes the malignant behavior of the Moser cells in vitro in terms of growth in soft agarose and invasion of Matrigel-coated porous membranes. Expressing antisense EGFR RNA in the Moser cells (through transfection with an inducible antisense EGFR expression vector) downmodulated the expression of cell surface EGFR and EGFR mRNA with a concurrent inhibition of growth in soft agarose and invasion of Matrigel-coated membranes. In addition, the ability of exogenously applied EGF in promoting the malignant behavior of these cells was circumvented. We conclude that antisense EGFR RNA was a potent agent in circumventing the in vitro malignant properties of the Moser cells.
Clin Exp Metastasis 1995 May
PMID:Expression of antisense epidermal growth factor receptor RNA downmodulates the malignant behavior of human colon cancer cells. 775 Feb 6

The epidermal growth factor receptor and its ligands have been implicated as being involved in normal mammary development and breast cancer genesis. Northern blotting was used to assay the mRNA levels of the epidermal growth factor receptor and three of its ligands: the epidermal growth factor, the transforming growth factor alpha and the Amphiregulin in 16 primary carcinomas, 2 metastases and 5 fibroadenomas. In addition, the mRNA levels of the other members of the epidermal growth factor receptor family, erbB2 and erbB3 were also analysed. We found limited expression in the breast carcinomas while all the fibroadenomas showed expression at high levels. Therefore we suggest that the epidermal growth factor receptor plays an important role in the development of fibroadenomas. The erbB2 and erbB3 were more strongly expressed than the epidermal growth factor receptor in the primary carcinomas. This suggests that they could be of importance in breast carcinogenesis.
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PMID:High expression of the EGFR in fibroadenomas compared to breast carcinomas. 784 1

Aggressiveness of follicular (FTC) and papillary thyroid cancer (PTC) varies widely. Tumorigenesis is associated with an imbalance of growth-promoting and growth-constraining factors. We investigated the effects of thyrotropin (TSH), epidermal growth factor (EGF) and transforming growth factor beta 1 (TGF-beta 1) on invasion and growth of 3 FTC- and 2 PTC-cell lines. Invasion (penetration through an 8 microns pore membrane, covered by Matrigel) and growth were measured using the MTT-method. EGF (10 ng/ml) and TSH in low concentrations (1 mU/ml) stimulated invasion and growth of FTC and PTC, whereas TGF-beta 1 (10 ng/ml) and TSH in high concentrations (100 mU/ml) were inhibiting. The parental cell line FTC133 was considerably more responsive to all growth factors than the metastatic clones. Invasion of FTC133 was enhanced by 42% (EGF) and 21% (TSH), invasion of FTC236 by 8% (EGF and TSH). Conversely, invasion of FTC133 was inhibited by 32% (TGF-beta 1) and 21% (TSH), invasion of FTC236 by 18% (TGF-beta 1) and 11% (TSH). TSH, EGF and TGF-beta 1 have an important impact on differentiated thyroid cancer cells and metastases may have developed by escaping from the normal control of growth factors.
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PMID:[Growth and invasion in differentiated thyroid carcinoma. Function of different growth factors]. 785 Nov 42

Organ cultures were established from 2-mm punch biopsies of human skin and maintained for 12 days in either serum-free, growth-factor-free basal medium or in medium supplemented with a number of epithelial cell growth factors including epidermal growth factor, insulin, hydrocortisone and pituitary extract. Normal histological architecture was preserved in growth-factor-free basal medium. However, in the presence of exogenous growth factors, the epidermis was thickened and hypertrophied. There was focal loss of the usual maturation progression, accompanied by abnormal keratinization patterns. In some areas, basement membrane disruption occurred and epithelial cells penetrated into the dermis in these areas. Isolated squamous epithelial cells and nests of cells could be clearly seen within the dermal stroma. In additional studies, an enzyme-linked immunosorbent assay was used to assess fibronectin and laminin production. Increased levels of both matrix components were seen in the culture fluids from tissues maintained under conditions which promote invasion. Taken together these findings indicate that growth-factor-stimulated normal squamous epithelial cells have the capacity to carry out functions that lead to concomitant synthesis and break-down of the underlying basement membrane and to invasion of mesenchymal tissue. This organ culture system may help to elucidate mechanisms of in situ invasion by squamous epithelial cells.
Invasion Metastasis 1993
PMID:In situ epithelial cell invasion in organ culture. 796 May 75

The aggressiveness of follicular thyroid cancer (FTC) varies widely, and metastasis is the primary cause of death. Uncontrolled proliferation of cancer cells may be associated with loss of growth factor control. We investigated the effects of stimulating (epidermal growth factor [EGF]; thyreotropin [TSH] in low concentrations) and inhibiting growth factors (transforming growth factor beta 1 [TGF beta 1]; TSH in high concentrations) on invasion and growth of FTC cell lines from the thyroid tumor (FTC133) and from the lymph node (FTC236) and lung (FTC238) metastases of the same patient. Invasion-penetration through an 8 microns pore membrane, covered by Matrigel (basement membrane)-and growth were measured using the MTT-method. EGF (10 ng/ml) and TSH in low concentrations (1 mU/ml) stimulated invasion and growth of all FTC cell lines, but the amplitude of stimulation differed significantly. The parental cell line FTC133 was considerably more responsive to growth factor stimulation than the metastatic clones. Invasion of FTC133 was enhanced by 42% (EGF; p < 0.02) and 21% (TSH; p < 0.01), invasion of FTC236 by 8% (EGF; p < 0.02) and 8% (TSH; p < 0.01), and invasion of FTC238 by 9% (EGF; p < 0.02) and 8% (TSH; p < 0.01). Conversely, invasion and growth of FTC133 were significantly more inhibited by TGF beta 1 (10 ng/ml) and supraphysiologic concentrations of TSH (100 mU/ml) than the cell lines from the lymph node and lung metastases. At day 7, invasion of FTC133 was inhibited by 32% (TGF beta 1; p < 0.02) and 21% (TSH; p < 0.01), invasion of FTC236 by 18% (TGF beta 1; p < 0.02) and 11% (TSH; p < 0.01), and invasion of FTC238 by 16% (TGF beta 1; p < 0.02) and 12% (TSH; p < 0.01). Moreover, we analyzed growth factor independence in minimally supplemented or unsupplemented medium. Growth, but no invasion was evident when cells were cultured completely unsupplemented over 7 days. These results suggest that metastatic FTCs may have developed by escaping from the normal control of TSH and other growth factors.
Clin Exp Metastasis 1994 Jul
PMID:Aberrations of growth factor control in metastatic follicular thyroid cancer in vitro. 803 5

Three stable carcinoma cell lines, designated RM22-F5, RM17-5R, and RM1-4, were established from spontaneously occurring mammary carcinomas in old, outbred, female Wistar rats. The RM22-F5 and RM17-5R cells were keratin-positive and formed epithelial monolayers, whereas RM1-4 cells exhibited a spindle-like morphology and intense vimentin staining. When injected into nude mice, RM22-F5, RM17-5R and RM1-4 cells formed well-differentiated, poorly differentiated and undifferentiated carcinomas, respectively. The relative growth rates of the tumor cells in vitro were RM1-4 > RM22-F5 > RM17-5R. The growth of RM22-F5, but not of RM17-5R and RM1-4 cells, was significantly stimulated by insulin, epidermal growth factor, dexamethasone, 17 beta-estradiol and progesterone in vitro. Ovariectomy reduced the growth of RM22-F5 cells in vivo and these cells (but not RM1-4 or RM17-5R) were estrogen-receptor (ER)-positive. None of the lines were positive for the progesterone receptor (PR). Spontaneous lung and lymph-node metastases were observed in nude mice injected with RM22-F5 or RM17-5R cells, respectively. In contrast, RM1-4 cells were non-metastatic but invasive. Karyotype analysis revealed that RM22-F5 cells were hyperdiploid, RM17-5R were hypotetraploid, and RM1-4 were diploid with a sizeable insertion in chromosome 1. A point mutation in codon 12 (G to A transition) and loss of the normal allele of the H-ras-1 gene was detected in the DNA from RM22-F5 cells. No p53 mutations were apparent in any of the cell lines. The results indicate that RM22-F5 cells are hormone-dependent with an ER+/PR- phenotype, while the RM17-5R and RM1-4 lines are hormone-independent and ER-/PR-. These cell lines exhibit the spectrum of biological properties and genetic alterations observed in human breast cancers and may, therefore, be novel and useful models for understanding sporadic breast cancer in post-menopausal women.
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PMID:Establishment of hormone-dependent and hormone-independent carcinoma cell lines with different metastatic potentials from spontaneous mammary tumors in aged Wistar rats. 805 57

Invasion and metastasis may be caused by the escape of tumor cells from the negative control of growth factors. We analyzed the effects of transforming growth factor-beta 1 (TGF beta 1) on growth, migration, invasion, and adhesion in three follicular thyroid cancer cell lines (FTC133, primary; FTC236, lymph node metastasis; FTC238, lung metastasis) from one patient and in a papillary line (PTC-UC3). Cell growth was measured by dimethylthiazol-diphenyltetrazolium bromide assays, and migration (basal or epidermal growth factor stimulated) was determined by the ability of cells to penetrate 8-microns pore membranes that were covered with Matrigel for invasion assays. Moreover, we studied tumor cell adhesion to collagen type IV, fibronectin, and laminin. TGF beta 1 inhibited growth in FTC (FTC133, by 31%; FTC236, 15%; FTC238, 17%; P < 0.008), but not in PTC. Migration was inhibited in all cell lines. TGF beta 1 inhibited epidermal growth factor-stimulated migration of FTC133 by 43% vs. 29% without epidermal growth factor (P < 0.03). TGF beta 1 also inhibited invasion (FTC133, 32%; FTC236, 18%; FTC238, 16%; PTC-UC3, 32%; P < 0.02). All cell lines adhered preferably to collagen type IV and fibronectin. TGF beta 1 enhanced adhesion. Again, these effects were less pronounced in the FTC metastases. In conclusion, TGF beta 1 inhibits the growth, migration, and invasion of thyroid cancer cells in vitro. It enhances adhesion to components of the extracellular matrix. Metastatic thyroid tumors may be less responsive to the negative regulation of TGF beta 1.
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PMID:Transforming growth factor-beta 1 is a negative regulator for differentiated thyroid cancer: studies of growth, migration, invasion, and adhesion of cultured follicular and papillary thyroid cancer cell lines. 807 65

Amphiregulin is a recently described member of the epidermal growth factor family. Primary breast cancers were assessed for expression of amphiregulin by immunochemistry (111 cases), Northern, and/or dot blots (68 cases). Epidermal growth factor and estrogen receptors were measured in all cases. p53 and erbB-2 expression was assessed by immunohistochemistry for most cases. There was no association of these factors with amphiregulin expression, which was detected by immunochemistry in 40 of 111 cases. A significant association of amphiregulin expression assessed by Northern dot blots versus immunochemical staining was seen (P = 0.0016). Expression was not detected in adjacent nontumor tissue by immunochemistry. Amphiregulin was expressed in tumor epithelium, but not stromal or inflammatory cells. Expression was more common in lymph node positive cases (23 of 49; 47%) than lymph node negative cases (11 of 42; 26%; P = 0.04). The coexpression of epidermal growth factor receptor and amphiregulin in 35% of epidermal growth factor receptor positive cases raises the possibility of an autocrine loop in this subset of patients. Amphiregulin stimulates fibroblast growth and is up-regulated in breast cancer. A possible effect on tumor stroma may relate to the association with metastases.
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PMID:Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer. 810 63

The plateau in survival rates from head and neck cancer as well as the increasing incidence of disease among various populations demands the need for new perspectives in head and neck oncology. In pursuit of that goal, investigators have been developing improved biologic markers for metastatic risk of head and neck cancer. Such markers can be placed into categorical groupings, of which markers for cellular differentiation may be the most relevant. Among the growth factors relevant to head and neck cancer, epidermal growth factor and its receptor have received the most attention. Those tumors with unregulated growth factor control tend towards a more dedifferentiated state. Additionally, the degree of cellular differentiation and resulting risk of metastases may be predetermined in an individual through constitutively expressed susceptibility genes. Polymorphisms of the L-myc oncogene identified within peripheral blood lymphocytes may represent such a marker. Certain polymorphisms of this gene will identify individuals likely to express dedifferentiated head and neck cancer. Finally, the expression of cell-surface differentiation antigens may govern the capacity of cell-mediated host immune systems to control metastatic growth.
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PMID:Biologic markers, cellular differentiation, and metastatic head and neck cancer. 812 18


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