Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 67-kd high-affinity laminin receptor (67 LR) is a gene product whose expression appears to be associated with the invasive and metastatic phenotype of a variety of human cancer cells. Northern blot hybridization has been routinely used to quantify the level of 67 LR mRNA from total cellular RNA extracts of homogenized tissue specimens or in vitro grown cell populations. This technique is useful to assess the average expression of the 67 LR mRNA of a particular sample but does not provide information about expression in specific cell types nor about heterogeneity of expression from cell to cell. In this study, we analyzed the expression of 67 LR mRNA in four human cancer cell lines with varying degrees of expression of 67 LR protein (renal cancer A-704, breast carcinoma MCF-7/4 and MCF-7/7, and pancreatic cancer Panc-1) using in situ hybridization performed with 67 LR riboprobes. Total cellular RNA was simultaneously extracted from the cell lines and hybridized on Northern blots with a 67 LR cDNA probe to assess the validity of the mRNA detection by in situ hybridization. Sixty-seven LR mRNA expression was higher in Panc-1 and MCF-7/4 cells than in MCF-7/7 and renal carcinoma A-704. There was a direct correlation (R2 = 0.88) between the in situ hybridization analysis and the mRNA levels detected by Northern blot analysis. The in situ hybridization method showed a heterogeneous expression of the 67 LR mRNA in the four cell lines with different subpopulations of cells showing a range from negative to high levels of the message. Sixteen freshly frozen human colorectal tissues (seven adenocarcinomas, five matched normal mucosae, and four adenomas) were also analyzed by in situ hybridization. The 67 LR mRNA was localized in normal and neoplastic epithelial cells. Adenocarcinoma cells showed a 1.6- to 5-fold higher expression (P < 0.02 according to the Wilcoxon-Mann-Whitney test) than did epithelial colonic cells from normal mucosae or adenomas. The signal tended to be stronger in poorly differentiated carcinomas and carcinomas with metastases than in moderately differentiated and nonmetastatic tumors. We conclude that the high expression of 67 LR mRNA in colorectal tumors is due to an increased production by tumor cells. Furthermore, in situ hybridization is an effective method to detect the expression of LR mRNA in cultured cell lines as well as in frozen tissue sections.
 ...
PMID:Detection of laminin receptor mRNA in human cancer cell lines and colorectal tissues by in situ hybridization. 144 45

In vitro invasion and in vivo metastasis assays were performed with a panel of MCF-7 cells transfected with isogenic constructs of mutated rasH genes. Both increased levels of rasH expression and rasH oncogene activation increased activity of derivative cell lines in in vitro invasion assays. In vivo formation of spontaneous metastases was assessed after intradermal inoculation of MCF-7 cells in the vicinity of the mammary fat pads of ovariectomized nude mice. No metastases were seen in the absence of estradiol treatment of the mice. With estradiol supplementation of the mice both the rasH-transfected and control transfected cell lines gave a higher incidence of metastases than parental MCF-7 cells. Prolonged treatment of mice with exogenous estradiol (60 days vs. 21 days) resulted in more frequent metastases to liver and lung at the end of the 90-day observation period. In contrast to activated rasH-gene enhancement of metastatic capacity of rodent fibroblast and epithelial cell lines, there was no correlation of rasH expression with in vivo metastatic capacity of a human mammary carcinoma cell line.
 ...
PMID:Invasive and metastatic properties of MCF-7 cells and rasH-transfected MCF-7 cell lines. 153 35

In order to investigate the estrogen metabolism in human breast cancer, the estradiol 2- and 16 alpha-hydroxylase (2-, 16 alpha-OHase) activities were determined in the microsomal fractions of human breast tissues by using reverse-phase HPLC. The effects of estrogen metabolites on the cell proliferation were also examined by employing two human breast cancer cell lines. The 2-OHase activity was detected in most cancerous and noncancerous tissues, but the value in cancerous tissues was significantly lower than that in noncancerous tissues (p less than 0.05). Patients without lymph node metastases showed relatively higher activity than those with metastases (0.05 less than p less than 0.1). The 16 alpha-OHase activity was, however, found in only 23% of cancerous tissues. Among those, the activity was present in 52% of ER positive cancerous tissues, but almost absent in ER negative ones. The growth ER positive cell line, MCF-7, was suppressed with 2-hydroxyestrone and stimulated with 16 alpha-hydroxyestrone. The cell proliferation stimulated with 16 alpha-hydroxyestrone was not inhibited by the addition of tamoxifen, a strong antagonist of estradiol. Two metabolites had no effect on the growth of ER negative cell line, MDA-MB-231. These results suggest that estrogen metabolites influence the proliferation of human breast cancer cells as the endogenous regulatory factors and should be considered for the future endocrine therapy.
 ...
PMID:[Biological effect of estrogen metabolites in human breast cancer]. 161 94

Laminin, a major basement membrane component, arrested the migration of MCF-7/AZ human breast adenocarcinoma cells that were not invasive in vitro. Migration of invasive MCF-7/6 cells was not affected by laminin. Both cell types expressed the 67 kD laminin receptor, at both mRNA and protein level, but did not express the alpha 6 subunit of the VLA-6 integrin-type laminin receptor. The presence of YIGSR peptides (100 micrograms/ml), reported to block the interaction between laminin and its 67 kD receptor, did not change the migratory response of MCF-7/AZ or MCF-7/6 cells when meeting laminin lanes. In addition, the migration of these cell types was not affected by the presence of 17-beta-estradiol (10(-6) M) or all-trans retinoic acid (10(-6) M), which were both reported to increase the number of 67 kD receptors. We could therefore not assign an involvement of the 67 kD receptors in migration of MCF-7 cells on laminin, nor did we find evidence that conditioned medium of MCF-7/6 cells contains factors that are able to initiate migration of MCF-7/AZ cells on laminin.
Clin Exp Metastasis
PMID:Arrest of MCF-7 cell migration by laminin in vitro: possible mechanisms. 183 8

Bone metastases in breast cancer may be osteolytic, osteosclerotic, or a mixture of the two. Although stimulation of bone resorption by breast cancer cells has attracted some interest, the formation of osteosclerotic secondary tumours and the influence of human mammary carcinoma cells on osteoblasts (bone forming cells), both important in understanding breast cancer--bone interactions, have been largely neglected. We therefore examined the effects of conditioned medium (CM) from two cultured human breast cancer cell lines (MCF7 and ZR-75) and from primary cultures of breast carcinomas from two patients, on osteoblasts and recruitment of bone-resorbing cells (osteoclasts) in vitro. Osteoblast-like cells (BDC) were cultured from human trabecular bone explants. Osteoclast maturation was studied in fetal rat calvaria cultured on collagen gels. CM from the MCF-7 line and cells derived from one patient each inhibited BDC DNA synthesis, but stimulated osteoclast recruitment. In contrast, CM from the second patient's cells or ZR-75 enhanced DNA synthesis in BDC, but blocked osteoclast maturation. This suggests that human breast carcinomas secrete soluble factors which influence both osteoclasts and osteoblasts. A further unexpected implication is that mammary carcinoma cells may cause local osteosclerosis by directly stimulating osteoblasts, rather than through raised bone turnover in metastases.
 ...
PMID:Breast carcinomas synthesize factors which influence osteoblast-like cells independently of osteoclasts in vitro. 200 8

Transfection of the immortalized human breast epithelial cells MCF-10A with the mutated ras oncogene resulted in cell transformation (MCF-10A-neoT). Since the transformed state is usually associated with enhanced migratory activity, increased capability to invade basement membranes and to grow in a three-dimensional basement membrane gel (growth in matrigel), we compared these properties in MCF-10A-neoT cells with those of MCF-10A cells transfected with either the neomycin resistance gene alone (MCF-10A-neo cells) or with the normal ras proto-oncogene (MCF-10A-neoN cells). MCF-10A-neoT cells exhibited enhanced migratory activity, as assessed by chemotaxis and chemokinesis assays. and increased capability to invade the basement membrane. These cells also formed large colonies in matrigel. MCF-10A-neo and MCF-10A-neoN cells, on the other hand, showed only marginal migratory, invasive and semisolid medium growth properties. These results indicate that the mutated ras oncogene induces in human breast epithelial cells phenotypic characteristics of malignant transformation.
Invasion Metastasis 1991
PMID:Increased invasive, chemotactic and locomotive abilities of c-Ha-ras-transformed human breast epithelial cells. 206 Oct 3

Malignant progression in breast cancer represents the processes through which localized, hormone-dependent tumor cells become resistant to endocrine manipulations and metastasize to sites distant from the primary tumor. By selection in ovariectomized athymic nude mice, we have isolated a variant (MIII) of the hormone-dependent, poorly invasive, human breast cancer cell line MCF-7. MIII cells have lost their absolute requirement for estrogen to form proliferating tumors in nude mice. Furthermore, these tumors are significantly more invasive than the parental MCF-7 cell line. MIII cells retain some responsivity to estrogens and antiestrogens, indicating that they have progressed to a hormone-independent but hormone-esponsive phenotype. In an attempt to determine the nature of this process, we have compared the phenotype of MIII cells with that of other MCF-7 variants. These comparisons strongly suggest that the factors contributing to perturbations in antiestrogen sensitivity, hormone-dependent growth, metastatic potential and tumorigenicity are essentially independent of each other and acquired in a random manner. Loss of estrogen receptor expression and overexpression of EGF receptors tend to occur later in the process of malignant progression.
 ...
PMID:The process of malignant progression in human breast cancer. 208 84

Metastases develop in 30% to 40% of patients with operable breast cancer. Investigators have reported on the detection of occult micrometastases in bone marrow using an antibody to epithelial membrane antigen (EMA) and have since reported prognostic significance for these antibody-detected cells. In this study, two anti-cytokeratin monoclonal antibodies (35 beta H11 and 34 beta E12) were used to examine bone marrow specimens from patients with breast cancer. The technique was first studied in a test system in which human or monkey bone marrow was seeded with MCF-7 cells, and was determined to be sensitive enough to detect fewer than one cancer cell in 10(4) hematopoietic cells. An immunoglucose oxidase method was used for patient specimen antibody localization and was found to be free of false-positive staining. Marrow specimens from 25 patients with breast cancer of various stages were examined. No correlation with disease stage was observed. We conclude that the technique is feasible, but prognostic import remains to be determined.
 ...
PMID:Monoclonal antibodies for detection of occult carcinoma cells in bone marrow of breast cancer patients. 247 Apr 94

In vitro attachment assays were carried out to assess adhesion between two basement membrane proteins, type IV collagen and laminin, and rat rhabdomyosarcoma (RMS) cell lines with different metastatic potentials. Whereas cells did not adhere to type IV collagen, adhesion to laminin appeared to be very sensitive as maximal adhesion was achieved in dose-response assays with only nanograms of laminin. Adhesion was mediated by interactions between coated laminin and cell surface components, probably receptors, but not endogenous laminin. Laminin-mediated adhesion of RMS cell lines was compared with that of the MCF-7 (human mammary carcinoma) and the L6 (rat myoblast) cell lines. In dose-response assays, RMS cell lines required 10 times less laminin to reach half-maximal attachment rates than MCF-7 and L6 cell lines. Two laminin fragments, P1 and E8, which are structurally and immunologically distinct as shown by alpha-helix content, SDS-PAGE and monoclonal antibody mapping, supported adhesion by RMS cells and L6 myoblasts, but MCF-7 adhered only to P1. This fragment was 10 times less active than laminin in RMS cell lines. Attachment in dose-response assays and adhesion inhibition studies by antibodies revealed that E8 accounted for the activity of laminin in RMS cell adhesion. Adhesion in the RMS cell lines was dominated by interaction with E8 regardless of metastatic potential.
Clin Exp Metastasis
PMID:Laminin-mediated adhesion in metastatic rat rhabdomyosarcoma cell lines involves prominent interactions with the laminin E8 fragment. 252 68

The samples of breast cancer and cell lines MCF-7 and ZR-75-1 were tested for the occurrence of cysteine proteinase inhibitors ACPI and NCPI. Further, the influence of estradiol on the expression of these inhibitors was examined. Both the tested inhibitors were found in tumor cells and in cell lines. Moreover, the positivity was found also in the connective tissue, especially in the vicinity of dysplastic changes and normal lobules. The expression of both the inhibitors can be regulated by estrogens. The data indicate a possible connection of NCPI expression with the regulation of cell proliferation and ACPI with cellular differentiation. The role of these inhibitors in invasive processes and metastases is not clear so far.
 ...
PMID:Demonstration of cysteine proteinase inhibitors ACPI and NCPI in breast cancer and in cell lines MCF-7 and ZR-75-1. 253 Aug 10


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