Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concanavalin A (Con A)-induced agglutinability of normal, preneoplastic, and neoplastic mouse mammary epithelial cells was examined. Cells freshly dissociated from normal mammary glands, hyperplastic alveolar nodules, or primary mammary adenocarcinomas by collagenase digestion in the presence of bovine serum albumin were strongly agglutinated by low concentrations of Con A. After short-term culture in vitro, however, cells from all three types of tissue were only weakly agglutinated by Con A, as measured by both suspension and hemadsorption assays. By comparison, cells of three established mammary tumor culture lines agglutinated strongly in the presence of the lectin. Treatment of the normal, preneoplastic, and neoplastic mammary cells in primary cultures with either trypsin or collagenase had little or no effect on their agglutinability, whereas hyaluronidase significantly increased their reactivity. Studies with fluorescein-tagged Con A indicated that all three cell types were capable of binding the lectin. The results were consistent with previous evidence suggesting that neoplastic transformation of mouse mammary epithelial cells is not manifested in vitro by several of the alterations in growth patterns, intercellular interactions, and surface properties that usually accompany transformation of fibroblastic cells.
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PMID:Concanavalin A-induced agglutinability of normal, preneoplastic, and neoplastic mouse mammary cells. 28 51

The application of flow cytometry to enrich airway epithelial cell subpopulations is described. A complementary epithelial cell preparative technique is also outlined. The ability of the airway epithelium to protect the lung from environmental insults results from a complex interaction among the different cells that form its matrix. The separation of the different epithelial cell types is an essential step in the studies of mechanisms of the controlling factors of cell repair, cell differentiation, and neoplastic transformation. Epithelial cells of the New Zealand white rabbit trachea are prepared using enzymatic digestion and microdissection. Small sections of tracheal wall are dissected into pieces approximately 10 mm2. The mucosa is dissected and placed in 0.15% hyaluronidase for 40 min at 22 degrees C. Mucus is removed, and the mucosa is then placed in 0.1% pronase at 37 degrees C for 30 min. With careful dissection, the epithelium can be dissected from the mucosa in 10-mm2 sheets. Sheets of epithelial cells are placed in 6 ml of an enzymatic solution containing collagenase, 0.2% bovine serum albumin, 0.04% soya bean trypsin inhibitor, 0.06 ml of 1 M Hepes buffer for 3 h at 37 degrees C. The cells are gently pipetted during the 3-h period, yielding a suspension of viable cells. Subpopulations of these different cell types are enriched using an Orthocytofluorograph 50111. A krypton ion laser was used for excitation of cells at 488 nm. Forward-angle and 90 degrees scatter were gated on the histogram. The purification of the ciliated, basal, and secretory cells was 90%, 97%, and 94%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enrichment of subpopulations of respiratory epithelial cells using flow cytometry. 184 47

In experimental animal models the susceptibility of the mammary gland to neoplastic transformation is related to its degree of development and proliferative activity; this observation led us to determine whether the human breast epithelium also exhibits development-related differences, and whether these differences could be detected in an in vitro system. Normal breast tissue obtained from reduction mammoplasties of 9 patients ranging in age from 18 to 56 years were characterized in both whole mount preparations and organoids obtained after collagenase-hyaluronidase digestion by their degree of development based upon the types of lobules present. Lobules were classified into type 1 (Lob 1), composed of approximately 11 alveolar buds, the less developed; lobules type 2 (Lob 2), of moderate development, composed of approximately 47 ductules each, and lobules type 3 (Lob 3), composed of 80 ductules each, represented the highest level of development. Epithelial organoids obtained after digestion were plated in DMEM:F12 medium supplemented with hydrocortisone, cholera toxin, insulin and 5% horse serum with a calcium concentration of 1.05 mM Ca++. Following attachment, the medium was replaced by medium containing 0.040 mM Ca++. The percentage of attachment of organoids to the flask was greater in cells from Lob 1 (89-99%) and Lob 1+2 (79-100%) than in cells from Lob 3, which had a 53-67% attachment. The total yield of cells after 7 weeks in culture was also greater in cells derived from Lob 1 and Lob 1+2 than in cells from Lob 3. The total yield of cells obtained from primary cultures was not related to the number of organoids plated, but to the degree of development of the gland. The DNA-labeling index (DNA-LI) in intact breast tissue correlated with that in primary cultures; it was greater in Lob 1 and Lob 1+2 than in Lob 3. By flow cytometry, the highest percentage of cells in S-phase was seen in cells with the highest DNA-LI. We concluded that the growth characteristics of mammary epithelial cells in vitro in a low Ca++ medium is modulated by the degree of development and differentiation of the gland.
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PMID:Influence of human breast development on the growth properties of primary cultures. 275 52

High-molecular-weight hyaluronan acts as a ligand of the tumor-suppressive Hippo signal, whereas degradation of hyaluronan from a high-molecular-weight form to a low-molecular-weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro-oncogenic transcriptional coactivator yes-associated protein (YAP), which creates a cancer-predisposing microenvironment and drives neoplastic transformation of cells through both cell-autonomous and non-cell-autonomous mechanisms. In fact, accumulation of low-molecular-weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor growth in vivo, pharmacological intervention of the Hippo-YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo-YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors.
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PMID:Hyaluronan Degradation Promotes Cancer via Hippo-YAP Signaling: An Intervention Point for Cancer Therapy. 3244 82