Lysosomes in cancer cells

Allison, A. C.

doi:10.1136/jcp.s3-7.1.43

Cited by 16 publications

(8 citation statements)

References 22 publications

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“…A summary of normal cellular glycosidase locations and function is illustrated in Figure 2. Alterations in lysosomal enzyme content, localization and/or function may result in cellular properties associated with oncogenic transformation and malignancy (27,29,30).…”

Section: Normal Role Of Cellular Glycosidasesmentioning

confidence: 99%

Glycosidases in cancer and invasion

1985

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Glycosidases have been demonstrated to be elevated in the interstitial fluid of tumors, sera of animals and patients with tumors, and in some tumor tissue as compared to normal adjacent tissue. Elevations of serum beta-N-acetylglucosaminidase and beta-glucuronidase most commonly have been found to occur and these enzymes have been shown to be secreted into the extracellular medium by many different tumor cell types in vitro. The mechanism of cellular release of these hydrolytic enzymes probably involves tumor lysosomal exocytosis. Increased tumor glycosidase levels may promote increased tumor cell shedding from primary tumors, local invasion and perhaps be responsible directly, or indirectly for structural changes in tumor cell surface glycoconjugates. These cell surface changes could facilitate tumor cell thrombus formation, secondary site implantation and attachment in the microcirculation to endothelial cells and/or subendothelial basement membrane components. Other studies have demonstrated a correlation between metastatic cell potential and increased endoglycosidase and polysaccharide lyase activity. Generally, metastatic tumor cell variants have been found to be more invasive and capable of degrading proteoglycan basement membrane components, in part due to these increased levels of degradative enzymes. Hence, it is of considerable interest to develop inhibitors against these enzymes. Initial studies with glucuronidase inhibitors in the therapy of bladder tumors have been promising and with the advent of better agents and the use of appropriate in vitro metastatic models it may be possible to design and develop agents which interfere in various metastatic events and limit tumor progression.

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Section: Normal Role Of Cellular Glycosidasesmentioning

confidence: 99%

Glycosidases in cancer and invasion

1985

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“…Since this article deals with the methodology of cluster analysis, presentation of results will be restricted to comparison of cells at the end of mitosis and to cells 12 h after mitosis, when they are actively engaged in DNA synthesis in view of the following division. Mitotic cells were chosen because in other cell types, several observations in light and electron microscopy suggested, on a qualitative basis, lysosome clustering at mitosis (Robbins & Gonatas, 1964;Allison & Mallucci, 1964;Allison, 1969;Erlandson & de Harven, 1971). Different degrees of clustering of lysosomes could thus be expected in cell populations sampled 40 min and 12 h after the removal of a metaphase block by Colcemid, which is considered as zero time.…”

Section: Experimental Modelmentioning

confidence: 99%

Application of cluster analysis for characterization of spatial distribution of particles by stereological methods

Baudhuin

Leroy-Houyet

Quintart

et al. 1979

Journal of Microscopy

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A method for the detection and characterization of clusters of particles observed in section with the electron microscope is presented. Cluster analysis is performed by the division method described by Berthet et al. (1976). Starting from a single cluster, profiles from each electron micrograph are successively classified in sets containing an increasing number of clusters. The decrease in the mean free distance, lambda, between profiles in the clusters, is used for terminating the subdivision procedure. The function relating the mean free distance with the number of clusters is evaluated in each subdivision set. The actual number of clusters is selected on the basis of the slope of that function, at a point where lambda has a value close to the average profile diameter. The method assumes a convex shape for the clusters; the salient feature is that it provides a physical delineation of clusters in the section. Hence, an evaluation of some characteristics of clusters in the three-dimensional sample may be obtained by using standard stereological procedures. Characterization of the volume to which the individual particles of a population are eventually restricted can as a result be performed. Practical problems in the acquisition of the data needed for cluster analysis are discussed and a system using for that purpose a Quantimet 720 image analyser in a basic configuration, connected on line with a PDP 11/10 minicomputer, is presented. Application of the method is illustrated by the analysis of lysosomes in cultured hepatoma (HTC) cells, at the end of mitosis and during the S phase. Cluster analysis shows that in cells actively synthesizing DNA they are grouped in clusters representing 5.7% of the cellular volume. Moreover, the average number of particles per cluster falls from a minimum of thirteen at mitosis to only six at the S phase.

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“…Many investigations have implicated the lysosomal acid hydrolases in tissue injury and degeneration (de Duve, 1959, Allison, 1969. Recently, several reports have emphasized the roles of lysosomal hydrolases in normal metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%