Some mechanisms involved in cancer cell detachment by necrotic material

Weiss, Leonard

doi:10.1002/ijc.2910220214

Cited by 37 publications

(17 citation statements)

References 25 publications

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“…Mitotic inhibitors have been extracted from the necrotic core (see, for example, Levine et ai, 1984), and these prc-sumably diffuse through the spheroid affecting the mjtotic behaviour of some of the cells; however, this mechanism alone cannot be responsible for saturation since it requires that all the cells be inhibited if a continued increase in volume due to cell reproduction is to be prevented; this contradicts experimental observations. During mitosis, the reduced strength in binding between cells may cause individual cells to be shed into the surrounding matrix (Weiss, 1978;Landry et al, 1981) however, the cells that remain will still be reproducing so this mechanism cannot explain growth saturation either. In the models of Greenspan (1972) and subsequent similar studies, the crucial parameter for saturation arises in an expression stating that the contraction rate of the necrotic core is proportional to its volume; it is suggested that this is due to the process of disintegration of necrotic cellular material into simpler permeable compounds with a subsequent loss in volume.…”

Section: Discussionmentioning

confidence: 99%

Mathematical modelling of avascular-tumour growth

Ward

1997

Mathematical Medicine and Biology

340

254

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A system of nonlinear partial differential equations is proposed as a model for the growth of an avascular-tumour spheroid. The model assumes a continuum of cells in two states, living or dead, and, depending on the concentration of a generic nutrient, the live cells may reproduce (expanding the tumour) or die (causing contraction). These volume changes resulting from cell birth and death generate a velocity field within the spheroid. Numerical solutions of the model reveal that after a period of time the variables settle to a constant profile propagating at a fixed speed. The travelling-wave limit is formulated and analytical solutions are found for a particular case. Numerical results for more general parameters compare well with these analytical solutions. Asymptotic techniques are applied to the physically relevant case of a small death rate, revealing two phases of growth retardation from the initial exponential growth, the first of which is due to nutrient-diffusion limitations and the second to contraction during necrosis. In this limit, maximal and 'linear' phase growth speeds can be evaluated in terms of the model parameters.

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Section: Discussionmentioning

confidence: 99%

Mathematical modelling of avascular-tumour growth

Ward

1997

Mathematical Medicine and Biology

340

254

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“…Increased activities of lysosomal enzymes in tumors correlate with tumor malignancy in vivo [8][9][10][11][12] but have often been attributed to the presence of infiltrating host cells or necrotic tumor cells [13,14]. This does not appear to be true for elevated activities of lysosomal proteinases as, in early studies, the highest lysosomal proteinase activities were shown to be associated with the youngest and most rapidly growing tumors [15,16].…”

Section: Lysosomal Cysteine Proteinasesmentioning

confidence: 99%

Plasma Membrane-Associated Cysteine Proteinases in Human and Animal Tumors

Sloane¹,

Rozhin

Hatfield

et al. 1987

Pathobiology

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The ability of tumor cells to invade into and through normal tissue during the metastatic cascade has been attributed to tumor-associated degradative enzymes including proteinases of the metallo, serine and cysteine classes. Work from several laboratories has established that the cysteine proteinases cathepsins L and B are released from tumor cells, primarily as latent precursor forms. In addition, a cathepsin B-like cysteine proteinase has been shown to be associated with the plasma membrane fraction of several animal and human tumors. This form of the enzyme retains activity under physiologic (or pathologic) conditions including at neutral pH and in the presence of low Mr inhibitors. Since we have established that cathepsin B can degrade the basement membrane attachment glycoprotein laminin, we speculate that plasma membrane-associated cathepsin B may participate in focal dissolution of the basement membrane during tumor cell extravasation.

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“…These effects were not due to the chemotactic activities of the extracts, because they were present on both sides of the membrane. Thus, while chemotaxis (necrotaxis; Bessis, 1973) is a factor which could contribute to the accumulation of macrophages around necrotic tissues as observed for example in the W-256 tumour (Weiss, 1978), the enhancement of migration observed by us is due to chemokinesis.…”

Section: Discussionmentioning

confidence: 86%

Some effects of products from necrotic regions of tumours on the in vitro migration of cancer and peritoneal exudate cells

Turner

Weiss

1980

Intl Journal of Cancer

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The invasion of normal tissues by cancer cells and the infiltration of tumours by macrophages to some degree involves active translatory movements by these cells. As necrosis is a common occurrence in solid tumours, we have studied the interactions of saline extracts from the necrotic regions of rat Walker-256 tumours and mouse Gardner lymphosarcomas on the transmembrane, in vitro migration of Walker and Gardner cancer cells, and rat and mouse peritoneal macrophages. Necrotic extracts enhanced cell migration independently of chemotactic activity, an effect which was partially reduced by Trasylol, an inhibitor of neutral proteases. Rat liver lysosomal preparations which contain lower levels of neutral proteases than necrotic extract, inhibited or had no effects on cell migration, and the lysosomal stabilizer hydrocortisone did not inhibit the action of necrotic extracts. The results indicate that necrosis may enhance the migration of cancer cells out of tumours and the migration of macrophages into them. The extracts act partially through their neutral protease content. In contrast to the enhancement of cell detachment by necrotic extracts, which previous work has shown to be partially mediated by their indirect effect in causing lysosomal labilization and which is partially inhibited by hydrocortisone, this indirect mechanism is not demonstrable in the enhancement of cell migration. The results indicate that the consequences of necrosis are worthy of consideration in attempts at understanding the biology of solid tumours.

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Some mechanisms involved in cancer cell detachment by necrotic material

Cited by 37 publications

References 25 publications

Mathematical modelling of avascular-tumour growth

Mathematical modelling of avascular-tumour growth

Plasma Membrane-Associated Cysteine Proteinases in Human and Animal Tumors

Some effects of products from necrotic regions of tumours on the in vitro migration of cancer and peritoneal exudate cells

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