The enhanced metastatic capacity of an in vivo selected Lewis lung tumor line (LLT-HH) was correlated with changes in cell-associated glycosaminoglycans (GAG) using ultrastructural cytochemistry, flow cytometry and biochemistry. The increase in highly sulphated GAG content on the cell membrane of LLT-HH cells compared to the parent LLT cells was demonstrated cytochemically. Using in vitro [3H]glucosamine labelling of GAG components it was shown that the LLT-HH cells were characterized by a high production of heparan sulphate while the parent LLT line had a high hyaluronic acid-chondroitin sulphate production. The high metastatic phenotype is accompanied by an altered production of cell-associated GAGs.

Animals↗

PubMedDate not supplied

Chemotherapeutic sensitivity of liver metastases from intrasplenically-growing Lewis lung tumor.

A recently developed metastatic tumor model was used to study the therapeutic response of liver metastases derived from intrasplenically growing LLT. Treatment was performed on the day following surgical removal of the 'primary tumor'. The life-span of tumor-bearing animals and the number and volume of liver metastases were measured. Cyclophosphamide and 13324 (a new bifunctional nitrosoureido derivative) proved to be most effective. Some other drugs (5-FU, MeCCNU, Lycurim) showed a temporary regression in the formation of macrometastases without influencing the life-span. Adriamycin was slightly more effective given i.p. than i.v.

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PubMedDate not supplied

Endothelialization of embolized tumor cells during metastasis formation.

The reaction of the endothelial barrier to tumor cell extravasation has been studied using electron microscopy. The model system was pulmonary metastases produced by intravenous injection of B16-F10 melanoma cells. A striking difference was observed in the behavior of the endothelial lining of arterioles versus that of capillaries. In capillaries, partial retraction of endothelial cells took place following the attachment of tumor cells. The tumor cells then immediately attached to the basement membrane and the basolateral surface of the retracted endothelial cells. The endothelial cells extended to cover the tumor cells prior to complete extravasation. In the arterioles, on the other hand, endothelial retraction did not occur following tumor cell attachment. Instead the attached tumor cell emboli became encompassed by endothelial cells, outgrowing from the intact endothelial lining of the arteriole. Owing to the proliferation of the tumor cells, tumor colonies encompassed by endothelial cells expanded within the lumen. When these intravascular growths completely filled the lumen, the tumor cells extravasated from the vessel only after the original endothelial layer became mechanically disrupted and the tumor cells thereby came into contact with the basement membrane.

Arterioles↗

PubMedDate not supplied

Demonstration of the organ preference of liver selected 'high metastatic' Lewis lung tumor cell line.

The experimental metastasis patterns of 'low metastatic' Lewis lung tumor (LLT) and liver selected 'high metastatic' LLT-HH were studied following their arterial dissemination. In previous reports it was shown that both tumor lines develop metastases only in the first encountered organ. Here the liver preference of the liver selected cell line is demonstrated. The model of two LLT cell lines can provide experimental evidence for both the 'mechanical' and 'seed and soil' theories of metastasis formation, depending on the site of tumor cell injection.

Animals↗

PubMedDate not supplied

Comparative study on Lewis lung tumour lines with 'low' and 'high' metastatic capacity. III. Glycosaminoglycan synthesis, transport and degradation in cell lines.

The glycosaminoglycans (GAGs) of low (LM) and highly metastatic (HM) cell lines of the Lewis lung tumour (3LL) were compared using [3H]glucosamine labelling techniques. The GAGs isolated from nuclei, cytoplasm, pericellular fractions and medium were analysed by cellulose acetate electrophoresis and by digestion with specific enzymes, and the following conclusions were drawn. 1. Increased cellular uptake and incorporation of [3H]glucosamine into glycoconjugates of the cytoplasm was a typical feature of the highly metastatic cell line after a 48-h labelling. However, there was no elevated radioactivity in glycolipids. 2. Radioactivity of the purified GAGs was two and three times higher in nuclear and cytoplasmic fractions of HM cells than in those of LM cells. There was much less difference between the two cell lines in the pericellular fractions. 3. A definite change from chondroitin sulphate to dermatan sulphate dominancy was recorded in each GAG fraction. Higher heparan sulphate labelling was observed in the cytoplasmic and pericellular GAGs of HM cultures. 4. In the post-labelling period about three times more GAG was present in the extracellular compartment of the HM cultures compared with the LM cultures. 5. In the LM cultures the total GAG-associated radioactivity decreased by 73 per cent in the 48-h chase period whereas in the HM cultures it decreased by only 30 per cent. This indicates a higher rate of GAG degradation in the LM cultures.

Biological Transport↗

PubMedDate not supplied

Expression of HLA-DR antigens on bileduct cells of rejected liver transplant.

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Adolescent↗