Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An organ culture method suitable for the maintenance of viable human breast cancer for at least 14 days has been described. This method was applied to a total of 94 breast cancer specimens. It allowed good survival of "soft" tumors of various histological types, with loose connective stroma even in hormone-free medium. In contrast, "scirrhous" cancers showed poor survival in hormone-free medium; viable cells were maintained only at the very periphery of the explants. Supplementation of the medium with insulin (10 mug/ml), ovine prolactin (5 mug/ml), and hydrocortisone (1 mug/ml) in various combinations seemed to induce enlargement of viable cancer cells and moderate loosening of the stroma in some cases. However, it did not improve the survival of central tumor cords in scirrhous explants. Further supplementation of the medium with 17 beta-estradiol (minimum effective dose, 0.1 to 10 ng/ml), although it did not affect soft tumors, markedly improved survival of the cancer cells of scirrhous tumors throughout the whole explants, with evidence of collagen digestion around the neoplastic cells. This was observed in 18 of 20 scirrhous cancers subjected to this treatment. Estradiol need not be present during the whole culture period; the results at 14 days were identical in explants treated with estradiol for the first 7 days only or for the entire period. Addition of purified collagenase during the first 24 or 48 hr of culture resulted in complete dissolution of the collage. After such treatment, culture under the usual conditions resulted in excellent survival of the explants without improvement from hormone supplementation; thus, while estradiol was necessary when collagen was present, it was not longer required after collagen digestion. It can be concluded that breast cancer cells in organ culture are only slightly, or not at all, hormone dependent for survival, provided that they are not restrained by a dense collagen barrier. The estrogen-induced changes allowing survival inside the scirrhous explants strongly suggest the presence of an estrogen-dependent collagenolytic enzyme system in the collagen-rich breast cancers. This system could represent an important component of the hormone dependency of human breast cancer growth.
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PMID:Estradiol-dependent collagenolytic enzyme activity in long-term organ culture of human breast cancer. 16 44

When cultured in-vitro, originating from different breast cancer patients, tumor cells, identified histologically as carcinoma cells, varied in their proliferation patterns and cell morphology. If exposed for brief periods to vibrio cholera neuraminidaes (VCN), the amount of sialic acid released from the cells varied from one culture to another and increased with higher enzyme concentrations. If exposed to trypsin, the amount of released proteins varied also from one culture to another. Significant difference was observed between the effect of VCN or collagenase on normal and neoplastic cell cultures. Whether human or murine cell cultures, the cell-free media harvested from cultures of neoplastic cells containing high concentrations of collagenolytic-caseinolytic-fibrinolytic and esterolytic activities. Two effects of concanavalin A (Con A) have been distinguished on thymidine incorporation, the first is a decrease in the maximal thymidine uptake, whereas the second is a shift to the maximum thymidine uptake to higher Con A concentrations. At low concentrations, alpha-1-antitrypsin (AAT) had no effect, but at high concentrations it inhibited 3H-thymidine uptake. At low concentrations human profibrinolysin inhibited and at higher concentration sit enhanced uptake of the labeled precursor. Therefore, the collagen olytic caseinolytic-fibrinolytic enzyme is a pacemaker for proliferation of human mammary carcinoma cells.
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PMID:Human mammary carcinoma cells. The enzyme pacemaker profibrinolysin. 31 26

A method has been developed for studying in vitro the cell proliferation kinetics of human breast cancer, Surgical specimens from primary tumors were studied in 56 patients. Viable cell suspensions for assay were obtained by the dissociation of tumor tissue with collagenase. Mean Labeling indices of 2.43 +/- S.D 2.05 and 4.48 +/- S.D. 3.73, respectiviely, were found after incubation with 3HTdR for 2 hours and 24 hours. Mean S-times of 21.9 +/- S.D. 4.3 hours were estimated by 3H and 14C-TdR double-labeling. The kinetic data have been validated by parallel labeling studies in vivo and in vitro in four patients. The processing of autoradiographs using gold latensification provided slides for kinetic analysis within 3 days. The assay offers a method that is useful in the planning and monitoring of drug therapy.
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PMID:A rapid in vitro method for measuring cell proliferation in human breast cancer. 33 86

The effect of a cAMP derivative (N6, O2-dibutyryl cyclic adenosine 3',5'-monophosphate: dBcAMP) on the cell cycle and on the synthesis of typical extracellular matrix (ECM) components, i.e. collagen and glycosaminoglycans (GAG), was studied in two hormone-responsive human breast cancer cell lines VHB-1 and MCF-7. The data showed that dBcAMP induced a decrease in the proportion of cells in S + G2 + M phases due to an increase of the non-cycling (G0 phase) cell number as revealed by the Ki-67 antigen immunocytochemical study. The collagen synthesis, estimated by [3H] proline incorporation into the cellular proteins followed by an enzymatic digestion with highly purified bacterial collagenase, was not modified by dBcAMP. In contrast, the GAG synthesis, analysed by [3H] glucosamine incorporation, was increased two-fold in the dBcAMP treated cells. As a comparison we also tested 4-hydroxy-Tamoxifen (4-OH-Tam) since it induces similar cell cycle perturbations as dBcAMP. However, we did not observe a stimulation of the GAG synthesis following 4-OH-Tam treatment. These data demonstrated that the increased GAG synthesis is due to cAMP and is not a consequence of perturbations in the cell cycle. We can therefore assume that the ECM modifications induced by dBcAMP may contribute to the growth inhibition of the hormone-responsive human breast cancer cells.
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PMID:cAMP effect on extracellular matrix synthesis in human breast cancer cells. 133 23

Plasminogen activators (PAs) convert plasminogen to plasmin by the cleavage of the Arg-Val bond. There are two distinct types of PA, tissue type (t-PA) released from the endothelial cells of the blood vessels and urinary type (u-PA) released from urinary tubules. u-PA was found to be released from activated macrophages and virally transformed cells. t-PA was also found to be released from breast cancer cells induced by carcinogens or melanoma cells. In structure, t-PA has a finger domain homologous to fibrin-binding domain of fibronectin and a growth factor domain homologous to the epidermal growth factor. u-PA has no finger domain but has a growth factor domain. It is proposed that PA may be important in tumor growth due to the stimulation of tumor cells through binding of growth factor domain to its receptor of tumor cells. Another hypothesis is that PA may activate procollagenase to collagenase, which digests collagen to facilitate tumor growth. We have measured the concentrations of t-PA and u-PA in plasma, urine and tumor tissues of patients with cancer of the digestive tract and patients with uterine or ovarian tumors. The results indicate that the concentrations of u-PA increased in urine, plasma and cancer tissues of patients with cancer of the digestive tracts whereas no increase was observed in t-PA levels. On the other hand, the concentration of t-PA increased mostly in plasma of patients with uterine and ovarian cancers, but t-PA levels in tissues did not increase in patients with uterine and ovarian cancer.
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PMID:Plasminogen activators: possible roles in cell proliferation. 250 84

Basement membranes serve as significant barriers to the passage of tumor cells but ones which metastatic cells can pass. This involves the production of a cascade of proteases leading to the activation of a specific collagenase that degrades the unique collagen network in basement membrane. Breast cancer cells, when estrogen dependent, show a requirement for estrogen for invasive activity. However, when these cells progress to an estrogen independent state and increased malignancy, they express an invasive phenotype constitutively. Studies with various anti-estrogens suggest that these responses are mediated via the estrogen receptor. Anti-estrogens lacking agonist activity suppress invasiveness as well as growth of the breast cancer cells.
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PMID:Factors regulating basement membrane invasion by tumor cells. 290 53

The tumorigenic properties of human rheumatoid arthritis synovial cells in culture were investigated. The synovial cells developed good colonies and secreted plasminogen activator (PA) and collagenase in the cell cultures, as do Hela cells. Since PA and progesterone receptor (PgR) are considered to be end products of estradiol action in breast cancer cells, the estrogen receptor (ER) and PgR content in these cells was also assayed. Large amounts of ER and PgR were detected in the synovial cells in culture, even though these cells are not targets for sex steroids. Study of the cytomorphologic changes in the synovial cells in culture revealed many characteristics generally observed in neoplastic cells. Whether any or all of these observations have any implication in prognosis or therapy in this disease remains to be studied.
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PMID:Expression of tumor cell properties in synovial cells in culture. 302 23

In an attempt to understand the mechanism by which estrogens stimulate cell proliferation and mammary carcinogenesis, metastatic human breast cancer cell lines (MCF7, ZR75-1) were found to secrete a 52,000 dalton (52K) protein under estrogen stimulation. Following its purification to homogeneity, the 52K protein was identified as a secreted procathepsin-D-like aspartyl protease bearing mannose-6-phosphate signals. This precursor displays an in vitro autocrine mitogenic activity on estrogen-deprived MCF7 cells and is able to degrade basement membrane and proteoglycans following its autoactivation. The total protease (52K + 48K and 34K) was detected and assayed by monoclonal antibodies and was found to be highly concentrated in proliferative and cystic mastopathies. In breast cancer, its cytosolic concentration appears to be correlated more to tumor invasiveness than to hormone responsiveness. The mRNA of the 52K protease accumulates rapidly following estradiol treatment, as was shown by Northern blot analysis with cloned cDNA. The 52K cathepsin-D-like protease is the first example of a lysosomal protease induced by estrogens in cancer cells. Results obtained using different approaches suggest that two cysteinyl cathepsins are also related to cell transformation and invasiveness. It has been proposed that cathepsin-B is involved in breast cancer and metastatic melanoma, and its regulation by estrogen has been shown in the rat uterus. Cathepsin-L corresponds to the major excreted protein (MEP) whose synthesis and secretion are markedly increased by transformation of NIH 3T3 cells with Ki ras and are regulated by several growth factors. In addition to secreted autocrine growth factors and to other proteases (plasminogen activator, collagenase), lysosomal cathepsins may therefore play an important role in the process of tumor growth and invasion as long as their precursor is secreted abundantly.
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PMID:Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? 331 45

Cell suspensions from 16 tumour-free axillary lymph nodes from breast cancer patients were prepared, using collagenase digestion to free the sinus histiocytes from the fibrous stroma of the nodes. The histiocytic cells so obtained were then characterized using four surface markers: Fc(IgG) receptors, C3 receptors, DR antigen and a macrophage-associated antigen (defined by the monoclonal antibody VEP-7). In addition phagocytosis was assessed using IgG-coated red cells, and both lysozyme and alpha-1-antitrypsin were localized by means of immunoperoxidase staining. The results demonstrated that the majority of sinus histiocytes carried surface macrophage markers, but that a minority displayed phagocytosis and the presence of lysozyme or alpha-1-antitrypsin.
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PMID:Sinus histiocytes in axillary lymph nodes from patients with breast cancer: macrophage characteristics and activation level. 351 7

Serum proteinase-like peptidases and proteinase inhibitor activities have been determined in 40 women with breast cancer at presentation and following total mastectomy. Activities of these enzymes have also been determined in homogenates of malignant (n = 13) and non-malignant (n = 11) breast tissue and benign breast lesions (n = 10). Following surgical treatment, the serum collagenase-like, cathepsin B-like and cathepsin H-like peptidase activities were significantly reduced. In addition, the activities of collagenase-like, cathepsin B-like and elastase-like peptidases were significantly higher in malignant breast tissue than in either non-malignant tissue from the same breast, or benign breast lesions. These findings are consistent with the suggestion that proteinases may have a role in tumour invasion.
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PMID:Serum and tissue proteinase-like peptidase activities in women undergoing total mastectomy for breast cancer. 620 Mar 27


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