ArticleClinical & experimental metastasis1998
A unique allogenic model of metastatic pheochromocytoma: PC12 rat pheochromocytoma xenografts to nude mice and establishment of metastases-derived PC12 variants.
Article in Clinical & experimental metastasis, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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0 citing papers in PubMed, 11 citations in OpenAlex.
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Authors and funding
6 authors at 3 institutions in 2 countries.
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Abstract
Local invasion and metastatic spread to distant sites are major causes of death in patients with malignant pheochromocytoma. Since appropriate in vivo models do not exist, little is known about the underlying mechanisms of tumor growth and invasion. We, therefore, developed an animal model of malignant pheochromocytoma and established organotropic metastatic variants of PC12 rat pheochromocytoma cells. PC12 cells were established as xenografts to BALB/c NCR-NU mice. Subsequent to development of tumors or metastases, primary cultures from local tumors, metastases to lymph nodes, lungs and liver were established. These were subcultured in vitro and reinjected for up to five successive in vivo/in vitro cycles. Xenografted PC12 cells grew tumors with a doubling time of 6.78 +/- 0.58 days during log phase of tumor growth, killing hosts within 5-12 weeks depending on the experimental conditions. Tumors reproducibly metastasized to lymph nodes and the lung. Spontaneous metastases to the liver were not observed, but were achieved by intrasplenic injection of parent PC12 cells. In vitro, the metastatic cell lines displayed striking differences in morphology, overall growth patterns and nutritional requirements as well as binding to purified extracellular matrix proteins compared to the parent cell line. In vivo, the metastatic variants showed marked enhancement of metastatic ability. This is the first report of PC12 rat pheochromocytoma cells to exhibit the malignant phenotype in vivo. We also established variant PC12 cell lines that preferentially metastasized to specific sites and that had acquired different in vitro behavior and ability to metastasize. This unique model system should be useful for further studies relating to the invasion and metastases of pheochromocytoma and may prove valuable for investigations of novel antineoplastic therapies in vitro and in vivo.
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