Biomedical subjects

R Bjerkvig

Publications and source records attributed to R Bjerkvig.

96 records · Page 6Linked to original sources

PubMedDate not supplied

Multicellular tumor spheroids in serum-free culture.

The serum-free culture of multicellular tumor spheroids from two rat (BT4c, BT5c) and two human (GaMg, D-54Mg) glioma cell lines is described. The spheroids were propagated in two different chemically defined media, showing differences in growth requirements between the human and rat cell lines. The spheroids from all the cell lines showed reduced growth rate as compared to spheroids maintained in serum supplemented culture. A change in spheroid morphology was observed for the D-54Mg cell line, indicated by a reduced occurrence of microvilli, increased pyknosis and cellular granularity. The other spheroids maintained their morphology in serum-free culture. For the D-54 Mg spheroids, flow cytometric DNA measurements showed that the serum-free growth conditions caused a drop in the DNA S-phase (6.4% vs. 12.3% in serum supplemented cultures). The cell cycle distribution was unchanged for the other cell lines tested. The present study provides the basis for using multicellular tumor spheroids in biological studies which are dependent on a detailed control with chemical environment.

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PubMedDate not supplied

Characteristics of human and rat glioma cells grown in a defined medium.

Human (D54Mg, GaMg) and rat (BT5C, BT4Cn) glioma cells cultured in a chemically defined medium showed reduced growth when compared to serum-supplemented medium. The BT5C cells changed from a flat epithelioid morphology to a more glia-like structure. The serum-free medium caused an aggregation of BT5C cells which spontaneously lost anchorage dependence and continued to grow in suspension as multicellular tumor spheroids. The BT4Cn and human cell lines did not show any change in morphology. Flow cytometric DNA measurements showed no change in ploidy for cells grown in serum-free medium. Cell cycle analysis revealed that the same proportion of cells were proliferating (S and G2M phase cells) in serum-free medium as compared to serum-supplemented medium. The reduced growth is probably due to increased cell cycle time.

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PubMedDate not supplied

Growth arrest and polyploidization induced by metahalone microtubule inhibitors on rat glioma cells in culture.

Two pyrimidine analogs (metahalones) NY 3163, NY 3170 have been tested for their effects on the growth of rat glioma cells in monolayer and in spheroid culture. Both substances have earlier been found to inhibit the microtubule system in malignant cells. In glioma cells, arrest of mitosis was accompanied by repeated cycles of DNA synthesis, leading to different levels of polyploidization up to 16 and 32 ploid cells. The effect was not reversible through a culture period of 4 days. Reduced ability of directional migration of cells on a plastic surface was seen for 16 days after exposure. The reaction to microtubule inhibitors seems to differ depending on the type of tumour cells, where some malignant cells have earlier been reported to escape mitotic arrest and proceed to the next G1 phase, in contrast to the present glioma cells which undergo polyploidization.

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PubMedDate not supplied

Laminin: a potential inhibitor of rat glioma cell invasion in vitro.

The lack of metastatic behaviour of primary glioma is poorly understood. A possible natural barrier accounting for this phenomenon may be the proteins of the extracellular matrix which are found in the basement membranes of the blood vascular system. This hypothesis is reinforced by the finding that glioma invasion in vitro using a syngeneic model system results in a lack of invasion of areas of target tissue which contain extracellular matrix proteins. The study was extended by examining the effect of the incorporation of these proteins during the formation of fetal rat brain cell aggregates and glioma spheroids and on the invasion of aggregates by tumour spheroids. Laminin was shown to reduce the size of the aggregates and spheroids during their formation while fibronectin and type IV collagen had no effect. Laminin also prevented the invasion of the tumour spheroid into the target aggregate and appeared to inhibit migration of glioma cells on laminin coated tissue culture plastic.

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PubMedDate not supplied

In vitro and in vivo models for the study of brain tumour invasion.

Since it is difficult to study the dynamic biological aspects of brain tumour invasion using histological sections of surgical biopsy and autopsy tissues, various laboratory systems have been devised. Animal models are less than ideal as chemically-induced brain tumours suffer from the fact that they have a low incidence and a long latency, while transplanted tumours grow predominantly by expansion, due to high proliferative activity, and not by diffuse local invasion as in human brain tumours. Various in vitro assays have, therefore, been established for both migration and invasion. These include the simple scratch technique in a confluent cell monolayer, the use of cloning rings and the "Transwell" modified Boyden chamber technique. More complex, three-dimensional culture model systems have also been developed, using chick heart, optic nerve or reaggregated fetal brain as "targets" for the invasion of neoplastic glia. Each method has yielded important information on the mechanisms which underlie brain tumour invasion. Moreover, individual microenvironmental factors may be modulated in these laboratory systems to determine their influence on the migration/invasion process.

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PubMedDate not supplied

The role of growth factors in the malignant and invasive progression of intrinsic brain tumours.

Although growth factors are acknowledged for their mitogenic activity, a number of other functions are fulfilled by such peptides. These include control of motile and invasive behaviour, angiogenesis and phenotype. Various growth factors including epidermal growth factor, fibroblast growth factor, platelet derived growth factor, transforming growth factor and vascular endothelial growth factor have been described in human glial tumours. These factors may act in either autocrine or paracrine loop systems to determine the malignant potential of intrinsic brain tumours. This review examines each of these factors and their various isoforms and outlines the influence they may exert on the behaviour of neoplastic glia. Moreover, the role of growth factors in the control of the various mechanisms which underlie diffuse infiltrative invasion, neovascularisation and proliferation are explored. Finally, the potential of growth factors and their receptors as therapeutic targets is considered.

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