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

Cloned BALB/c 3T3 cells transformed in vitro with polyoma virus and maintained in culture (C cells) were compared with respect to their ability to form experimental metastases, with cells from the same clones that were passaged subcutaneously in vivo (CTC cells), thereby gaining a high tumorigenicity phenotype. No correlation was found between a high subcutaneous tumorigenicity potential or the progression state of these cells, and their capacity to form experimental metastases. Both cell types were also tested for their ability to release heparan sulfate degradation products from a naturally produced, sulfate-labeled extracellular matrix (ECM). Whereas the in vitro maintained C cells did not express an endo-beta-D-glucuronidase (heparanase) activity, some of the in vivo passaged CTC cells expressed such an activity. No strict correlation was found, however, between heparanase activity and the ability of CTC cells from individual tumors to form experimental metastases. However, A9 CTC 220 cells which produced a large number of lung metastases also expressed a high heparanase activity. Both heparanase and lung colonization by A9 CTC 220 cells were inhibited to a large extent by heparin, suggesting the involvement of heparanase in the extravasation of these highly metastatic cells. A9 CTC 220 cells were found to release basic fibroblast growth factor (bFGF) from ECM. This release was partially inhibited by carrageenan lambda which also completely inhibited the heparanase activity expressed by these cells. The in vivo acquisition of heparanase activity was not a result of cell fusion between heparanase expressing host-derived cells and heparanase-negative transformed cells. This conclusion was based on the fact that both the in vitro maintained, heparanase-negative as well as the in vitro passaged, heparanase-positive cells exhibited a similar membrane and molecular market profile.
Invasion Metastasis
PMID:Lung colonization by and heparanase activity in in vitro transformed 3T3 cells rendered highly tumorigenic by an in vivo passage. 765 21

Heparanase activity correlates with the metastatic potential of lymphoma, melanoma and mammary adenocarcinoma cell lines. We investigated the ability of various modified species of heparin and size-homogeneous oligosaccharides derived from depolymerized heparin to inhibit (1) heparanase-mediated degradation of heparan sulfate in a naturally produced subendothelial extracellular matrix (ECM), and (2) lung colonization of B16-BL6 melanoma cells in C57BL mice. Inhibition of heparanase was best achieved by heparin species containing 16 or more sugar units and having sulfate groups at both the N and O positions. Low-sulfate oligosaccharides were less effective heparanase inhibitors than medium- and high-sulfate fractions of the same-size saccharide. While O-desulfation abolished the heparanase-inhibiting effect of heparin, O-sulfated, N-substituted (e.g. N-acetyl or N-hexanoyl) species of heparin retained high inhibitory activity. Potent inhibitors of heparanase activity were also efficient inhibitors of tumor invasion and lung colonization. Heparin fractions with high and low anticoagulant activity expressed similar high antiheparanase and antimetastatic activities. Structural requirement for the inhibition of melanoma cell heparanase and lung colonization by species of heparin were different from those identified for (1) release of ECM-bound basic fibroblast growth factor (b-FGF) and (2) stimulation of b-FGF receptor binding and mitogenic activity. These results indicate that various nonanticoagulant species of heparin and other polyanionic molecules differing in size, sulfation and substituted groups can be designed to elicit specific effects resulting in the inhibition of cell invasion in tumor metastasis and autoimmunity, or stimulation of neovascularization and wound healing.
Invasion Metastasis
PMID:Inhibition of tumor metastasis by heparanase inhibiting species of heparin. 765 22

Transplantation of the human ovarian adenocarcinoma cell line, NIH:OVCAR-3 into athymic mice produces two morphologically distinct tumor cell populations (ascites and solid tumors). In the present study, we isolated both tumor cell phenotypes and investigated their relative malignant potential. Since cytoskeletal and morphological changes correlate with metastatic phenotype, expression of the intermediate-filament protein vimentin was compared between ascites and solid tumors. Ascites tumor cells showed a less differentiated epithelial morphology and concurrently expressed higher levels of vimentin. Ascites cells were more efficient in anchorage independent growth when compared with their solid tumor counterpart. Ascites tumor cells were also highly motile compared with the solid tumor cell population (P = 0.006). Migration of ascites tumor cells was further enhanced by type IV collagen, hyaluronic acid, and chondroitin sulfate A. Solid tumor cells removed from the same animal, however, were not significantly affected by these agents. From these studies, we conclude that ovarian cancer cells present in ascites are phenotypic variants which are highly motile compared with solid tumor cells isolated from the same animal. Ascites tumor cells with increased motility may contribute to peritoneal seeding and metastasis.
Clin Exp Metastasis 1995 May
PMID:Phenotypic variations and differential migration of NIH:OVCAR-3 ovarian carcinoma cells isolated from athymic mice. 775 Feb 4

Statistics from a 64 case study showed that mucinous adenocarcinoma was apt to invade the intestinal wall and to metastasize to lymph nodes (P < 0.05). The activity of arylsulfatase and lysozyme of mucinous adenocarcinoma was stronger than that of the papillary and tubular adenocarcinoma (P < 0.05). In RR staining for electron microscopic observation, a significant decrease of proteoglycan granules was found in the surrounding matrix of mucinous adenocarcinoma, which correlated with the amount of arylsulfatase and lysozyme secreted by mucinous adenocarcinoma. These enzymes reduced the degree of sulfation in heparan sulfate and degraded proteoglycans. The proteoglycan structural barrier having been destroyed, facilitates mucinous adenocarcinoma to infiltrate and metastasize.
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PMID:[A study on the mechanism of invasion of colorectal mucinous adenocarcinoma]. 787 65

A 45-year-old man presented with gynecomastia, hypertension and a large left adrenal mass. Further evaluation revealed elevated serum concentrations of estrogen, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, deoxycorticosterone, and aldosterone and increased 24-hour urinary 17-ketosteroid and free cortisol excretion. Removal of a 10 kg adrenocortical carcinoma led to normalization of the hormone concentrations and partial resolution of the gynecomastia. There was no clinical evidence of metastases. Incubation of tumor slices demonstrated that the tumor had an active aromatase and sulfotransferase. We estimated that about half the serum estrone arose from peripheral conversion of androstenedione. Feminizing adrenocortical carcinomas are rare and this case is unusual given the lack of clinical metastases and the probable dual source of estrogen from tumor as well as from the peripheral conversion of tumor-derived androgens.
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PMID:Feminization as a result of both peripheral conversion of androgens and direct estrogen production from an adrenocortical carcinoma. 793 Mar 80

Glycosaminoglycans were metabolically labeled in subconfluent cultures of highly metastatic 7Gp122 and poorly metastatic IC8 variants and of the low metastatic parental M4Be human melanoma cell line. Proteoglycans were separated by DEAE Trisacryl chromatography from the culture medium, from the heparin extract of the cell layer and from the heparin-extracted cell residue lyzed with detergents. Glycosaminoglycans were released from the proteoglycans by reductive alkaline hydrolysis and heparan sulfate (HS) was detected by deaminative cleavage with nitrous acid. Expressed on cell protein basis, the labeled HS content in the medium and in the cell layer decreased with increasing metastatic ability. The extraction of HS with heparin from the 7Gp122 cells indicated that this variant was enriched in (polypeptide bound) HS non inserted into the plasma membrane, compared with the low metastatic IC8 and M4Be cells. The HS fraction in heparin extract and in the heparin-extracted cell residue exhibited molecular mass heterogeneity on gel permeation chromatography and it contained HS fragments. Scission with nitrous acid followed by molecular sieve chromatography of the degradation products indicated that the tetra- and disaccharide repeats separated by the N-sulfated glucosamine residue were present in about equal amounts and constituted 60% of the HS chains in the IC8 and M4Be cells. HS from 7Gp122, IC8 and M4Be cells did not bind antithrombin III with high affinity but it was capable of binding bFGF in in vitro assay.
Clin Exp Metastasis 1993 Nov
PMID:Accumulation of heparan sulfate in the culture of human melanoma cells with different metastatic ability. 822 94

The expression of metalloproteinases, such as type IV collagenase/gelatinase, enables tumor cells to degrade type IV collagen present in the basement membrane and correlates with metastatic potential of several tumor types. We found that increased levels of rat serum type IV collagenolytic activity are associated with increased 13762NF mammary adenocarcinoma metastases in lungs and lymph nodes of syngeneic rats. To investigate serum metalloproteinases responsible for type IV collagenolysis, we performed zymography and Western blot analysis of rat sera. A M(r) 92,000 progelatinase (progelatinase B, M(r) 92,000 type IV procollagenase, MMP-9) was detected on zymograms of rat sera within 16 days after intramammary fat pad inoculation of highly metastatic MTLn3 cells. The activated serum M(r) 92,000 progelatinase degraded sodium dodecyl sulfate-denatured type I and IV collagens but was not active on casein, albumin, hemoglobin, and immunoglobulin. Sera from rats with fat pad tumors and lung metastases formed from highly metastatic clones possessed greater than 7 times higher levels of serum M(r) 92,000 progelatinase than control sera or sera from rats bearing similar size fat-pad tumors of low or nonmetastatic clones. The results were confirmed by Western blot analysis of rat sera using rabbit anti-human M(r) 92,000 progelatinase antibodies. Similar results were obtained from the analysis of rat plasma samples. The serum and plasma M(r) 92,000 progelatinase levels correlated with the extent of metastases in the lung and lymph nodes. The results indicate that high levels of serum and plasma M(r) 92,000 progelatinase are associated with the presence of disseminated metastatic adenocarcinoma cells and suggest that this enzyme may facilitate the invasion of blood-borne tumor cells through vascular basement membranes.
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PMID:Serum and plasma M(r) 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. 824 39

Adrenal androgens contribute 40% of total androgens in adult men. The inactive precursor steroids dehydroepiandrosterone (DHEA) and DHEA-sulfate are secreted in large amounts by the adrenals and reach the prostate and other peripheral target tissues, where they are transformed into the potent androgen dihydrotestosterone (DHT). We have cloned and sequenced the cDNAs and/or genes which encode the enzymes responsible for the transformation of DHEA into DHT, namely 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase, 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase. Blockade of DHT synthesized by these enzymes, with a pure antiandrogen of the class of flutamide, prolongs life in advanced prostate cancer, the effect being much more important when a small number of metastases is present. Most importantly, 3-month combination therapy reduces cancer-positive margins at radical prostatectomy, from 38.5% in control patients to only 13% in those who received combination therapy. Combined with an efficient strategy for detection of early-stage prostate cancer, the present approach could offer the possibility of a cure to more than 80% of prostate cancer patients, compared with the present situation where a cure can be offered to less than 20% of patients, since the first diagnosis of prostate cancer is usually made at a late stage of the disease.
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PMID:Intracrinology: the basis for the rational design of endocrine therapy at all stages of prostate cancer. 826 32

Despite undergoing a curative resection, many patients with colorectal cancer will develop and die of metastatic disease. It has been shown clinically and experimentally that surgery causes a transient period of immunosuppression, and it is postulated that this may encourage both the implantation of surgically disseminated tumor cells and the growth of existing micrometastases. The present study used natural killer cell cytotoxicity (NKCC) and tumor burden to evaluate perioperative modulation of immunocompetence in a murine model. We measured NKCC and tumor burden responses to a standardized surgical stress (SSS) alone, and to either morphine sulfate (MS) (15 mg/kg subcutaneously x 4 doses), ketorolac (a prostaglandin synthetase--prostaglandin E2--inhibitor) (2.5 mg/kg subcutaneously x 4 doses), or interleukin 2 (2,000 units intraperitoneally x 3 doses) administration with the SSS. In this model, we found that both low-dose interleukin-2 (IL-2) and ketorolac reversed the NKCC suppression associated with surgery, whereas morphine resulted in further depression of NKCC. In addition, IL-2 significantly decreased tumor incidence, whereas continuous MS exposure markedly increased tumor burden after surgery. These data suggest that IL-2 and ketorolac may be effective agents for the restoration of perioperative immune competence, whereas the use of continuous morphine might have significant deleterious effects.
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PMID:Perioperative immunomodulation in cancer surgery. 831 Nov 30

The fetoacinar pancreatic (FAP) protein is a specific component of the human exocrine pancreas associated with the differentiation and proliferation of acinar cells. FAP expression is enhanced in cases of pancreatic exocrine cancer and it is found in relatively high concentrations in pathological pancreatic juices. However, tumor cell lines do not secrete FAP into the culture medium. In this paper we analyze the intracellular localization of FAP in cell lines and compare some biological properties of the tumoral FAP with the normal adult and fetal forms. Immunocytological experiments performed using Mab J28 which characterizes FAP, gave a staining pattern suggestive of FAP localization in the ER. Subcellular fractionation corroborated this localization and established that FAP is tightly associated with the microsomal membranes. The absence of reactivity of the tumoral FAP with wheat germ agglutinin lectin and its strong reactivity with concanavalin A is consistent with the idea that FAP in tumor cells does not reach the Golgi apparatus and it is consequently retained in the endoplasmic reticulum (ER). FAP contained in hepatic metastasis derived from pancreatic adenocarcinoma appeared to be similar, if not identical, to that expressed by cell lines. This supports the hypothesis that FAP retention in the ER of malignant cells is a physiological phenomenon and not the result of a modification of cell lines due to the culture conditions. FAP expressed by cancer cell lines and metastases appeared by sodium dodecyl sulfate polyacrylamide gel electrophoresis a homogeneous protein with a M(r) of 120,000. Instead, the secreted mature protein consists of a main component of M(r) 110,000 and shows pronounced polymorphism (dispersion from M(r) 110,000 to 80,000). Increased size of the ER-retained protein is likely due to elongation of the peptide chain. Defective processing in the ER as a result of amino acid mutation could therefore explain the behavior of this protein in tumors.
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PMID:Retention of the fetoacinar pancreatic (FAP) protein to the endoplasmic reticulum of tumor cells. 846 90


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