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

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

In order to study the effect of estrogens and antiestrogens on the adhesive properties of human breast cancer cells, the attachment on endothelial cells (EC), on subendothelial extracellular matrix (ECM) and on ECM components (collagen I and IV, laminin, fibronectin) of estrogen-dependent (MCF-7, ZR75-1) and estrogen-independent (BT-20) breast cancer cell lines was investigated. The cells were grown under conditions of controlled exposure to estrogen [17 beta-estradiol (E2)] and/or antiestrogens [tamoxifen (Tam) or 4-hydroxytamoxifen (OH-Tam)]. Treatment by E2 enhanced the ability of ZR75-1 cells to adhere to the various substrates, which contrasts with the observed absence of effects with the BT-20 cells. Similarly, Tam or OH-Tam induced a reduction of the adhesion of ZR75-1 tumor cell, but not of BT-20 cells. This effect was reversed by competing concentrations of E2. The effects on MCF-7 cell adhesion were similar to those described for ZR75-1 cells, but could not be reproducibly observed. Adhesion assays carried out with ZR75-1 cells grown in the absence or presence of phenol red, a pH indicator which behaves as a weak estrogen, led to a similar pattern of cell attachment. Conditioned media harvested from E2- or Tam-treated ZR75-1 cells failed to induce any effect on adhesion of other ZR75-1 cells grown in E2-deprived medium, suggesting that secretory activities are not required for the control of cell adhesiveness. The results suggest that estrogens and antiestrogens can control the adhesive behavior of breast tumor cells through their hormone responsive structures possibly by regulating expression of cell adhesion proteins and/or their cell surface receptors.
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PMID:Modulation of human breast cancer cell adhesion by estrogens and antiestrogens. 270 28

We have previously demonstrated that confluent fetal fibroblasts migrate into three-dimensional collagen gels to a significantly greater extent than their normal adult counterparts. Recent studies have revealed that this behavioral difference results from the secretion by fetal fibroblasts of a soluble migration-stimulating factor (MSF) which acts on these cells in an autocrine fashion. Adult fibroblasts do not produce MSF but remain responsive to it. Skin fibroblasts from cancer patients resemble fetal fibroblasts (rather than normal adult cells) with respect to their migratory behavior on collagen gels and continued production of MSF. This communication is concerned with elucidating the biochemical basis of MSF activity. Data are presented indicating that a) hyaluronic acid is required for the elevated migratory activity displayed by confluent fetal and breast cancer patient skin fibroblast; b) adult fibroblasts exhibit a bell-shaped dose-response to MSF, with maximal stimulation of migration observed at a concentration of 10 ng/ml; c) the migratory activity of adult fibroblasts pre-incubated with MSF remains high in the absence of additional factor: and d) MSF affects both the quantity and size class distribution of hyaluronic acid synthesized by adult fibroblasts. We have previously speculated that the persistent fetal-like fibroblasts of breast cancer patients play a direct role in disease pathogenesis by perturbing normal epithelial-mesenchymal interactions. The observations reported here suggest that MSF-induced alterations in hyaluronic acid synthesis may contribute to the molecular basis of such perturbations.
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PMID:Mechanism of action of the migration stimulating factor produced by fetal and cancer patient fibroblasts: effect on hyaluronic and synthesis. 276 34

Exaggerated acute and late effects were observed in three of four women with pre-existing collagen vascular disease (CVD) within 2 years after definitive megavoltage radiation therapy for breast carcinoma. Five women with breast carcinoma, who developed CVD 3 months to 10 years after radiation therapy, had no complications. An abnormally severe reaction was observed during treatment of one patient with discoid lupus. The patient developed moist desquamation that persisted for a month, requiring early termination of treatment. One year after treatment, the patient developed paresthesias in the ipsilateral arm. A planned reduction of the prescribed dose in a second patient with progressive systemic sclerosis did not prevent intense erythema at the end of treatment, followed 14 months later by chest wall necrosis, which eventually required multiple surgeries including chest wall resections. The third patient, who had systemic lupus erythematosis, developed necrosis 2 years after treatment, which progressed over 12 years to osteoradionecrosis of the clavicle, sternum and rib cage. Multiple surgeries to repair the defect were complicated by flap necrosis and pleurocutaneous fistulas. The fourth patient died 6 months after radiotherapy without apparent sequelae. None of the patients had evidence of recurrent carcinoma. A history of collagen vascular disease appears to be a contraindication to breast conservation or for elective irradiation for breast cancer.
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PMID:Consequences of breast irradiation in patients with pre-existing collagen vascular diseases. 277 73

Fetal and normal adult skin fibroblasts show distinctive migratory behaviour when plated on three-dimensional collagen gels. Skin fibroblasts from 13 of 15 patients with hereditary breast cancer showed fetal-like behaviour compared with only 1 of 12 age-matched healthy controls (p less than 0.015; Wilcoxon signed-rank matched-pairs test). In addition, 10 of 15 first-degree relatives of patients with hereditary breast cancer showed a fetal-like fibroblast phenotype, compared with none of 7 surgical controls (p less than 0.009; chi 2 test). These results suggest that abnormalities expressed by skin fibroblasts may help identify people at increased risk of breast cancer developing.
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PMID:Fibroblasts from relatives of patients with hereditary breast cancer show fetal-like behaviour in vitro. 288 52

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 authors studied the distribution and the composition of collagen in neoplastic tissue from mastectomy specimens of 15 patients treated for an infiltrating ductal carcinoma NOS, in comparison to normal tissue of the opposite quadrant. The study was performed by light microscopy, microspectrophotometry, and electrophoretic methods. The results demonstrate a characteristic stromal organization of breast cancer in relation to collagen type I content.
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PMID:Collagen in human breast cancer: morphological and biochemical study. 302 Nov 87

We compared the effects of defined medium, fetal bovine serum (FBS) and human serum (HuS) on the growth and responses to chemotherapeutic agents of human breast cancer cells in primary culture. Normal and tumor tissues were dissociated to small aggregates and single cells and seeded onto collagen-gel-coated wells in defined medium or medium supplemented with 5% FBS or 5% HuS. In all cases examined, defined medium and medium containing HuS were superior to medium containing FBS in supporting growth of both normal and tumor cell cultures. However, cultures in defined medium showed an initial cell loss. Cells from the same tumor cultured in different media varied in their responses to chemotherapeutic agents. In light of these results, medium supplemented with HuS, which promoted attachment of these cells in culture and stimulated their growth, should be the most appropriate nutrient environment for determining the effects of therapeutic agents on cells as it most closely resembles the in vivo situation. Because there were also variations in growth rates and chemosensitivities of tumor cells cultured in different human serum samples, we suggest that optimal conditions in which to culture these cells include the serum of the patient whose tumor is removed. This serum may provide host factors that influence cell growth and interact with exogenous factors.
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PMID:Effects of defined medium, fetal bovine serum, and human serum on growth and chemosensitivities of human breast cancer cells in primary culture: inference for in vitro assays. 302 11

This paper underlines the interrelations between tumoral cells and the extra-cellular matrix in breast cancers with possible applications for the diagnosis and the prognosis. In mammary carcinomas, the first step of tumoral invasion is characterized by the loss of basement membrane components, particularly type IV collagen and laminin. Immunohistochemical detection of these disruptions of basement membrane is easy and useful for the diagnosis of "in situ" or microinvasive carcinomas. Laminin seems also to facilitate the adhesion of cancer cells to type IV collagen, and the dosage of its fragment P1 in the blood serum may be a good marker for the follow up of the patients. Stromal reaction involves many intricate macromolecules of the extra-cellular matrix. Types I and III collagens are often present in non colloid carcinomas. Rate, turn over of elastin and its prognostic value are still debated. Elastosis is related to well differentiated carcinomas and the presence of estrogen receptors. The stroma of the colloid form of breast cancer is rich in proteoglycans. Malignant and stromal cells, through the intermediary of cytokines, can synthesize these macromolecules. Hyaluronic acid and chondroitin sulfate are abundant in mammary carcinomas and form a favorable substrate for the growth and the migration of malignant cells. However, proteases decrease and limit their action. The presence of fibronectin, principally in the stroma, is difficult to interpret but fibronectin seems to play a role in tumoral retraction.
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PMID:[Breast carcinomas and the extracellular matrix]. 304 83

Evidence based on ultrastructure and immunocytochemical staining suggests that morphological gradations between epithelial and myoepithelial cells, and possibly between epithelial and alveolar-like cells, can occur in terminal ductal structures of rat and human mammary glands. In neoplastic disease the benign, carcinogen-induced rat and benign, human mammary tumours can contain epithelial, myoepithelial-like and alveolar-like cells, whereas their malignant counterparts mainly contain only epithelial-like cells. Clonal epithelial cell lines from normal rat mammary glands, from benign tumours and from SV40-transformed human mammary cultures can differentiate to either myoepithelial-like or alveolar-like cells. In those of the rat, the differentiation processes occur in steps, intermediate cells along the myoepithelial-like pathway resemble the morphological intermediates in the terminal ductal structures in vivo. Changes in specific polypeptides characterize each of the intermediate cells in vitro. One of the earliest increases observed in the myoepithelial-like pathway in vitro is that due to a novel protein p9Ka, whereas the major increases in Thy-1 antigen and the basement membrane proteins laminin and type IV collagen occur at later steps. The nucleotide sequence of the gene for p9Ka is related to that of the small, regulatory calcium-binding proteins, and antibodies raised to synthetic fragments of its predicted amino acid sequence react with only myoepithelial cells within the rat mammary parenchyma. Increases in the production of p9Ka and Thy-1 are largely due to increases in their messenger RNAs, possibly arising at the level of transcription of the DNA, whereas the increases in production of laminin and type IV collagen occur at a post-transcriptional level. The normal transcriptional promoter sequences of TATA or CAAT are not found adjacent to the genes for p9Ka or Thy-1. Cells and cell lines from malignant rat mammary tumours of increasing metastatic potential and from malignant areas of human ductal carcinomas largely fail to yield fully differentiated myoepithelial-like or alveolar-like cells in culture; however, weakly metastasizing rat cells yield variants which may retain a vestige of the myoepithelial phenotype. It is suggested that novel regulatory transcriptional element(s) may control the production of some of the proteins along the normal myoepithelial-like pathway, and that these elements may be relatively unique in their capacity to become inoperative in the malignant breast cancer cell.
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PMID:Stem cells in mammary gland differentiation and cancer. 307 45


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