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Pfragner, Roswitha; Behmel, Annemarie; Smith, Dana; Ponder, Bruce A.J.; Wirnsberger, Gerhard; Rinner, I.; Porta, S.; Henn, Traudl; Niederle, Bruno

doi:10.1023/a:1006959625068

Cited by 21 publications

(9 citation statements)

References 42 publications

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“…Attempts at developing human pheochromocytoma cell lines have not been successful, most likely due to the limited life spans of normal human cells in culture [14]. Establishing cell lines from normal tissues and benign tumors is challenging, since telomere shortening and lack of cell cycle augmentation derived from the characteristic of the transformed phenotype thwart long-term propagation.…”

Section: Introductionmentioning

confidence: 99%

Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor

et al. 2013

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BackgroundPheochromocytomas are rare tumors generally arising in the medullary region of the adrenal gland. These tumors release excessive epinephrine and norepinephrine resulting in hypertension and cardiovascular crises for which surgery is the only definitive treatment. Molecular mechanisms that control tumor development and hormone production are poorly understood, and progress has been hampered by the lack of human cellular model systems. To study pheochromocytomas, we developed a stable progenitor pheochromocytoma cell line derived from a primary human tumor.MethodsAfter IRB approval and written informed consent, human pheochromocytoma tissue was excised, minced, dispersed enzymatically, and cultured in vitro. Primary pheochromocytoma cells were infected with a lentivirus vector carrying the catalytic subunit of human telomerase reverse transcriptase (hTERT). The hTERT immortalized cells (hPheo1) have been passaged >300 population doublings. The resulting cell line was characterized morphologically, biochemically and for expression of neuroendocrine properties. The expression of marker enzymes and proteins was assessed by immunofluorescence staining and immunoblotting. Telomerase activity was determined by using the telomeric repeat amplification protocol (TRAP) assay.ResultsWe have established a human pheochromocytoma precursor cell line that expresses the neuroendocrine marker, chromogranin A, when differentiated in the presence of bone morphogenic protein 4 (BMP4), nerve growth factor (NGF), and dexamethasone. Phenylethanolamine N-methyltransferase (PNMT) expression is also detected with this differentiation regimen. CD-56 (also known as NCAM, neural cell adhesion molecule) is expressed in these cells, but CD31 (also known as PECAM-1, a marker of endothelial cells) is negative.ConclusionsWe have maintained hTERT-immortalized progenitor cells derived from a pheochromocytoma (hPheo1) in culture for over 300 population doublings. This progenitor human cell line is normal diploid except for a deletion in the p16 region and has inducible neuroendocrine biomarkers. These cells should be a valuable reagent for studying mechanisms of tumor development and for testing novel therapeutic approaches.

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Section: Introductionmentioning

confidence: 99%

Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor

et al. 2013

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Section: Pheochromocytomamentioning

confidence: 99%

“…In the late 1990s, two groups reported the establishment of human pheochromocytoma cell lines, termed KNA and KAT45, respectively (Pfragner et al 1998, Venihaki et al 1998. Both cell lines were derived from sporadic pheochromocytomas and were clearly bona fide chromaffin cells, showing a close morphological resemblance to PC12 cells (Pfragner et al 1998) (Fig. 1), with supporting evidence based on the production of catecholamines (Venihaki et al 1998) or the expression of markers including chromogranin A, human neurofilament protein, S100 and NSE (Pfragner et al 1998).…”

Section: Pheochromocytomamentioning

confidence: 99%

Advances in paraganglioma–pheochromocytoma cell lines and xenografts

Bayley

Devilee

2020

Endocrine-Related Cancer

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This review describes human and rodent-derived cell lines and xenografts developed over the last five decades that are suitable or potentially suitable models for paraganglioma-pheochromocytoma research. We outline the strengths and weaknesses of various models and emphasize the recurring theme that, despite the major challenges involved, more effort is required in the search for valid human and animal cell models of paraganglioma-pheochromocytoma, particularly those relevant to cancers carrying a mutation in one of the succinate dehydrogenase genes. Despite many setbacks, the recent development of a potentially important new model, the RS0 cell line, gives reason for optimism regarding the future of models in the paraganglioma-pheochromocytoma field. We also note that classic approaches to cell line derivation such as SV40-mediated immortalization and newer approaches such as organoid culture or iPSCs have been insufficiently explored. As many existing cell lines have been poorly characterized, we provide recommendations for reporting of paraganglioma and pheochromocytoma cell lines, including the strong recommendation that cell lines are made widely available via the ATCC or a similar cell repository. Basic research in paraganglioma-pheochromocytoma is currently transitioning from the analysis of genetics to the analysis of disease mechanisms and the clinically-exploitable vulnerabilities of tumors. A successful transition will require many more disease-relevant human and animal models to ensure continuing progress.

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“…A continuous cell line, KNA, was established from a sporadic pheochromocytoma of a 73-year-old woman [122]. The KNA cells grow as suspensions of spheroids and show the morphological and immunocytochemical characteristics of neuronal chromaffin cells, such as NE granules, and positive reactions to chromogranin, neuron-specific enolase and VIP antibodies.…”

Section: Chromaffin Cell Tumor Cell Linesmentioning

confidence: 99%

The Role of Cell Lines in the Study of Neuroendocrine Tumors

2012

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Cell lines originating from neuroendocrine tumors (NETs) represent useful experimental models to assess the control of synthesis and release of different hormones and hormone-like peptides, to evaluate the mechanisms of action of these agents in target tissues at the cellular and subcellular levels, and to study cell proliferation and tumor development, as well as the effect of different drugs on these complex processes. To date, the understanding of NET biology (with regard to their mechanisms of hormone secretion, cell proliferation and metastatic spread) has been hampered by the lack of appropriate animal models or cell lines for their study. In the present review, we aim to summarize the recent in vitro/in vivo data regarding cell lines derived from NETs which are most frequently employed in experimental neuroendocrinology.

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Cited by 21 publications

References 42 publications

Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor

Progenitor Cell Line (hPheo1) Derived from a Human Pheochromocytoma Tumor

Advances in paraganglioma–pheochromocytoma cell lines and xenografts

The Role of Cell Lines in the Study of Neuroendocrine Tumors

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