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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant cystosarcoma phylloides (CP) is a relatively rare cancer of the breast. A CP tumor was processed as part of a tumor acquisition, propagation, and preservation program in patient biotherapy. Two tissue culture cell lines were developed from this tumor, one directly from the biopsy, another from a xenograft tumor grown in athymic mice. The two cell lines were similar in character. There was strong immunochemical reactivity with antibodies to vimentin, type I collagen, and type III collagen. There was no reactivity with antibodies to cytokeratin and epithelial membrane antigen. Both cell lines were aneuploid, clonogenic in soft agar, and tumorigenic in nude mice. 5 alpha-dihydrotestosterone and thyroxine added to the culture medium stimulated growth, while testosterone, 17 beta-estradiol, and 4-hydroxytamoxifen were without effect. Dexamethasone and cortisol were inhibitory at high doses (10(-6) M). Dibutyryl cyclic AMP, theophylline, and vitamin C were all inhibitory. The biopsy contained tumor-infiltrating lymphocytes which proliferated in cultures containing interleukin 2. The expanded lymphocytes were activated T cells which had the capacity to lyse tumor cells. These results suggest possibilities in the therapy of cystosarcoma phylloides involving vitamin C, certain hormones, and tumor-infiltrating lymphocytes.
Breast Cancer Res Treat 1990 Dec
PMID:Cultured breast cystosarcoma phylloides cells and applications to patient therapy. 196 88

In this study we observed the incidence of hormone sensitivity in the response of MCF-7 cells to estrogen stimulation when the cells were cultured in different contact environments (hydrophilic plastic, bovine corneal extracellular matrix, type I collagen and in suspension culture). The major purpose was to describe the influence of cell to cell and cell to substrate contacts on the morphological response to estrogen treatment. However, other parameters including growth and induction of progestin receptor were also explored, keeping in mind that the MCF-7 cell line, although representative of normal mammary epithelium in that it contains a similar hormone receptivity, was selected in vitro from a metastatic population in a pleural effusion. Although substrate conditions did not modify growth enhancement by estrogens, progestin receptor levels were significantly higher in three-dimensional spheroid cultures in which cell to cell contacts were optimal due to elimination of basal contact. A careful morphological survey of large surfaces lead to an objective opinion of the overall effect of the hormone treatment on the non-cloned cell line in which a marked heterogeneity in the response of individual cells was observed. In terms of morphofunctional differentiation, the edification of acini with dense microvillus coating was best in suspension culture. When sections were made perpendicular to the plane of cultures on collagen gel rafts two other phenomena were noted: decrease in intercellular junctions, resulting in reduced cell to cell cohesion, and accumulation biodegradation products in the collagen lattice. This suggested a hormone-mediated interaction between the metastatic cells and the fibrillar substrate, collagen I, one of the major constituents of tissue stroma. This estrogen response might be related to the metastatic phenotype and must be distinct from their hormone sensitivity in terms of growth and differentiation since hormone receptivity is generally considered to be a favorable prognosis for breast cancer.
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PMID:Estrogen response of MCF-7 cells grown on diverse substrates and in suspension culture: promotion of morphological heterogeneity, modulation of progestin receptor induction; cell-substrate interactions on collagen gels. 652 40

Stromelysins are a group of proteases which degrade the extracellular matrix and activate other secreted proteases. Stromelysin (ST)-1 and ST-2 genes are induced by tumor promoters, oncogenes and growth factors, and have been involved in acquisition of the malignant phenotype. We show here that the thyroid hormone (T3) increases ST-1 and ST-2 expression in a non-transformed mouse mammary epithelial cell line (EpH4) in a way that is dependent on the level of thyroid receptor/c-erbA (TR alpha-1) expression. In agreement with this, T3 increases the secreted stromelysin activity and enhances the gelatinolytic activity of type IV collagenase. We have also demonstrated that T3 affects the epithelial polarity of EpH4 cells, diminishing the transepithelial electrical resistance of monolayers cultured on permeable filters, causing an abnormal distribution of polarization markers and the disruption of the organized 3-D structures formed by these cells in type I collagen gels. These results indicate that the ligand-activated TR alpha-1 plays an important role in regulating the morphogenetic and invasive capacities of mammary epithelial cells. Because the c-erbA locus is altered in several types of carcinoma, an altered or deregulated TR alpha-1 expression may also be important for breast cancer development and metastasis.
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PMID:Thyroid hormone regulates stromelysin expression, protease secretion and the morphogenetic potential of normal polarized mammary epithelial cells. 772 Jul 5

Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasiveness in vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasive in vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2 in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may exist in vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.
Breast Cancer Res Treat 1994
PMID:Collagen induced MMP-2 activation in human breast cancer. 788 Nov 12

We have already reported that stromal fibroblasts of breast cancer tissue (CaF) promoted the growth of breast cancer cells in vitro. It was found that CaF and fibroblasts in normal breast tissue (NF) showed the different growth and contracting activity. Materials were obtained from cancer tissue and normal breast tissue. Cells were prepared by collagenase digestion. The CaF's growth was more rapid than NF's. After a reconstitution of type I collagen, monolayer cultures of CaF and NF were done on collagen gel for 24 hours, then collagen gel was detached from the dish and was being float. After 2 days incubation, an area of collagen gel was measured. A contraction of CaF's gel was greater than that of NF. This showed that CaF had more contracting activity than NF. These results might be indicated that the function of CaF was to contribute the invasive growth of breast cancer cell as well as to secrete the growth factors. Therefore, it is considered, a control of the fibroblasts derived from cancer stroma may play an important role in the treatment of breast cancer.
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PMID:[Different growth rate and contracting activity of collagen gel between fibroblasts from breast cancer tissue and normal breast tissue]. 833 24

The present studies were aimed at determining if the use of a cell culture medium that supports proliferation of human mammary epithelial cells of the luminal lineage would allow routine isolation of breast cancer cells from primary and metastatic tumor specimens. Results obtained with mammary epithelial cells derived from reduction mammoplasty specimens and primary breast carcinomas indicated that growth of cells on type I collagen-coated dishes in Ham's F-12 medium supplemented with insulin, hydrocortisone, epidermal growth factor, cholera toxin, and 5% fetal bovine serum resulted in the growth and serial passage of cells that stained positively for the luminal cell marker cytokeratin 19. By contrast, growth of mammary epithelial cells in a growth factor-supplemented serum-free medium resulted in the emergence of mammary epithelial cell colonies that were uniformly negative for keratin 19. Filter isolation methods were used to isolate individual keratin-19-positive colonies from primary cultures derived from breast cancer specimens. All of the luminal mammary epithelial cells isolated from breast cancer tissues expressed characteristics of normal cells. Keratin-19-positive colonies isolated from several different tumors all grew rapidly for 30 to 60 days in culture and then senesced. Cells were isolated from one tumor that was known to have undergone a loss of heterozygosity at a specific locus in the p53 gene. All colonies isolated from this specimen contained both p53 alleles, which was consistent with their origin from normal luminal cells. Cells were also isolated from one tumor in which the c-erbB2 protein was drastically overexpressed in the neoplastic cells. Once again, keratin-19-positive colonies isolated from this tumor did not overexpress the c-erbB-2 protein. Experiments were then performed with cells derived from pleural effusions and metastatic lymph nodes. Results obtained with these specimens indicated that the growth conditions that support the growth of normal luminal mammary epithelial cells do not support the growth of neoplastic cells. However, the omission of cholera toxin, epidermal growth factor, and type I collagen substratum resulted in the isolation of two long-term cell lines. Both cell lines have population doubling times of approximately 100 h, are hyperdiploid, and stain positively for cytokeratin 19. Thus, culture conditions that support the growth of normal luminal mammary epithelial cells do not, in general, support the growth of breast cancer cells.
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PMID:Differential isolation of normal luminal mammary epithelial cells and breast cancer cells from primary and metastatic sites using selective media. 842 98

Following our recent finding that calmodulin antagonists can reduce cancer cell attachment to extracellular matrix proteins, we investigated the calmodulin antagonistic and anti-attachment properties of the non-steroidal anti-oestrogens tamoxifen and droloxifene. These drugs and four of their active metabolites were found to have calmodulin antagonist activity with IC50 values of 2-4 microM and to be capable of inhibiting attachment of murine B16 melanoma to extracellular matrix proteins in vitro. IC50 values for inhibition of attachment were 11 microM for tamoxifen and ranged from 5 to 40 microM for the other five compounds tested. (Poor reproducibility in drug potency between attachment experiments was almost certainly due to the low aqueous solubility of these drugs.) The effects of tamoxifen on cell/matrix adhesion were most evident between 15 min and 3 h of cell attachment. No effects of tamoxifen were evident in cells which had been allowed to attach for 6 h or more. Tamoxifen at concentrations between 0.1 and 30 microM was without effect on intracellular free calcium concentration. Tamoxifen also inhibited attachment of human ocular melanoma cells and human breast cancer (MCF7) cells to type I collagen. The concentration at which tamoxifen and its metabolites affect cell attachment in vitro (2-14 microM) is of the same order as the tissue concentrations of these drugs achieved clinically. The possibility exists that reduction of cell/matrix interactions may contribute to the clinical anti-metastatic efficacy of tamoxifen and some of its active metabolites.
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PMID:Inhibition of melanoma cell/matrix interaction by tamoxifen. 847 39

A panel of bone turn-over markers was assessed in 75 normocalcemic patients bearing bone metastases from breast cancer (BC), and in 25 advanced/metastatic BC patients without clinical appearance of bone involvement. 115 healthy women, stratified in three subgroups according to age served as controls. Bone formation was investigated by measuring serum carboxyterminal propeptide of type I procollagen (PICP), Bone Gla Protein (BGP, osteocalcin), bone isoenzyme of alkaline phosphatase (BALP); bone resorption by measuring serum carboxyterminal telopeptide of type I collagen (ICTP), fasting urinary hydroxyproline/creatinine (OHPro/Cr) and calcium/creatinine (Ca/Cr). In patients with bone metastases the percent of supranormal values (higher than mean plus 2 SD of the age-matched controls) ranged between 25% and 40% for indices of bone formation, about 73% for both ICTP and OHPro/Cr and about 30% for Ca/Cr. The median levels of all bone turn-over markers were higher in bone metastatic patients than in those without apparent skeletal involvement, but significance was attained only for OHPro/Cr, Ca/Cr and BALP. Supranormal levels of ICTP and OHPro/Cr were also found in about 65-70% of patients without apparent skeletal involvement. ICTP and Ca/Cr significantly correlated with bone pain score, BALP, ICTP, Ca/Cr significantly correlated with the number of tumour appearances in bone. In conclusion, the bone resorption indices, ICTP and OHPro/Cr, are much more frequently elevated than bone formation indices in BC patients with or without skeletal involvement. Their potential use in the early detection of bone metastases is hampered by the insufficient knowledge on specificity. Among the biochemical markers evaluated, Ca/Cr, ICTP and BALP, due to correlation with clinical aspects, appear the most interesting for follow-up studies.
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PMID:Biochemical picture of bone metabolism in breast cancer patients with bone metastases. 866 81

Measurements of biochemical markers specific to bone resorption are known to be useful in evaluation of skeletal metastasis. However, most of previous studies were performed cross-sectionally and sensitivity for detection of early bone metastasis was not satisfactory. Since basal levels of bone markers differ significantly individually, longitudinal studies would be preferable to evaluate small metabolic changes such as in early skeletal metastasis. Thus, we performed serial measurements of serum c-terminal telopeptide of type I collagen (ICTP), a bone resorption marker, in patients with malignancy and evaluated its clinical significances for detection of bone metastasis, comparing with measurements of propeptide of type I procollagen (PICP) and tumor markers. In total, 43 patients (41 of them are breast cancer), serial serum samples were obtained during 0.5 to 2.4 years (mean 1.4 years). In all of nine patients, who developed bone metastasis, serum ICTP level increased, and by successful treatment to the metastatic lesions, ICTP level decreased, while in some cases, tumor markers remained to be elevated. PICP was less sensitive and specific for detection of bone metastasis. Thus, serial measurement of ICTP is suggested to be useful for detection and evaluation of therapeutic responses in patients with bone metastasis.
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PMID:[Detection of bone metastasis by serial measurement of C-terminal telopeptide of type I collagen in patients with malignancy]. 868 82

The most abundant protein in bone is type I collagen. During type I collagen formation two extension peptides from both ends of the procollagen molecule, carboxy- and aminoterminal propeptides (PICP and PINP), are liberated in equimolar concentrations into the circulation. Type I collagen carboxyterminal telopeptide (ICTP) is formed during bone collagen breakdown and is liberated into the circulation. Serum concentration of the propeptides reflect bone formation, and the concentration of the telopeptide, bone resorption. We evaluated the usefulness of these bone remodelling markers in diagnosing and monitoring metastatic bone disease in breast cancer patients. Serum concentrations of ICTP, PICP and PINP were measured and the PICP/PINP-ratio calculated in 25 patients with bone metastases, 12 patients without metastases and their age matched healthy controls. S-ICTP and S-PINP were significantly higher in metastatic patients (p = 0.0001 and 0.02 respectively), and the S-PICP/PINP-ratio lower (p = 0.002) than in controls. S-PICP in metastatic patients did not differ significantly from that of controls. ICTP values in patients without metastases also differed from those of controls (p = 0.01). The clinical sensitivity for diagnosing metastatic bone disease was 56% for ICTP, 24% for PICP, 30% for PINP and 52% for PICP/PINP ratio. The clinical specifities were 93%, 100%, 98% and 91% respectively. During follow-up the changes in the marker values were parallel to the behaviour of the disease. We conclude that these markers alone are not sensitive enough for diagnosis, but they seem to be of use in detecting bone metastases and monitoring the activity of bone disease.
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PMID:Serum concentrations of type I collagen carboxyterminal telopeptide (ICTP) and type I procollagen carboxy-and aminoterminal propeptides (PICP, PINP) as markers of metastatic bone disease in breast cancer. 869 58


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