PC12 cells differentiate into chromaffin cell-like phenotype in coculture with adrenal medullary endothelial cells.

Mizrachi, Yossi; Naranjo, José R.; Levi, Ben‐Zion; Pollard, Harvey B.; Lelkes, Peter I.

doi:10.1073/pnas.87.16.6161

Cited by 30 publications

(17 citation statements)

References 34 publications

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“…PC12 cells are derived from a rat pheochromocytoma tumor able to differentiate into mature chromaffinic cells or into sympathetic neuronlike cells, depending on the external stimuli [Greene and Tischler, 1982;Guroff, 19851. Besides this property, this cell line is rich in bioactive peptides such as opioid peptides, neurotensin, and dynorphin, whose level are modulated during differentiation to one or another phenotype Byrd et al, 1987;Mizrachi et al, 1990;Margioris et al, 19921. We hypothesized that if EOPA acts as a bioactive peptide metabolizing enzyme: (1) we would be able to detect its presence in PC12 cells; (2) since the level of bioactive peptides changes according to PC12 differentiation, we inferred that EOPA activity would also be modulated during differentiation to one or another pathway.…”

Section: Nh2) Is Cleaved Generating [Met51-enkephalinmentioning

confidence: 98%

Characterization of an endooligopeptidase A‐like protein in PC12 cells: Activity modulation by cAMP but not by basic fibroblast growth factor

Ferro

Tambourgy

Abreu

et al. 1995

J of Cellular Biochemistry

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Endooligopeptidase A is a putative neuropeptide-metabolizing enzyme. It converts small enkephalin-containing peptides into the corresponding enkephalins and inactivates biopeptides such as bradykinin and neurotensin in vitro. We investigated the presence of endooligopeptidase A in PC12 cells. This cell line was derived from a rat pheochromocytoma tumor and resembles fetal chromaffin cell. Depending on the supplements added to the cell culture, this cell line can be differentiated into mature chromaffin cell or sympathetic neuron-like cell. Endooligopeptidase A activity was measured in soluble cellular extracts using a specific fluorogenic substrate QF-ERP7. The PC12 endooligopeptidase A-like activity shared similar but not identical biochemical properties with rabbit brain endooligopeptidase A. Similarly to rabbit brain endooligopeptidase A, the PC12 endooligopeptidase A-like activity was enhanced by DTT, totally inhibited by DTNB and 1-10 Phenanthroline, partially inhibited by cFP-AAF-pAb, and not affected by PMSF. Furthermore, the PC12 endooligopeptidase A-like activity displayed identical elution profile as rabbit brain endooligopeptidase A in gel filtration and anion-exchange chromatography. In addition, an antiserum raised against rabbit brain endooligopeptidase A cross-reacted with a 71 kDa component from PC12 cell extracts in Western blotting and was also able to partially neutralize the PC12 endooligopeptidase A-like activity. Treatment of PC12 cells with basic fibroblast growth factor (bFGF), a neurotrophic factor for this cell line, did not modify the specific activity of this enzyme. However, cAMP analogs decreased the specific activity of the enzyme. These results indicate the presence of an endooligopeptidase A-like activity in PC12 cells which is modulated by cAMP but not by bFGF.

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Section: Nh2) Is Cleaved Generating [Met51-enkephalinmentioning

confidence: 98%

Characterization of an endooligopeptidase A‐like protein in PC12 cells: Activity modulation by cAMP but not by basic fibroblast growth factor

Ferro

Tambourgy

Abreu

et al. 1995

J of Cellular Biochemistry

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“…Indeed, cancer cell/stromal cell interaction plays a crucial role in tumor growth and evolution, affecting gene transcription, differentiating and apoptotic pathways (Mauro et al 1994;Inouc et al 2001;Dong-Le Bourhis et al 1997;Lin et al 1998), though little is known about the mechanism through which host cells interfere with cancer growth; cell-to-cell communication-mediated tumor growth inhibition appears to be very tissue-specific, and it should also be borne in mind that host-tumor interaction is not a one-way process (Krutovskikh 2002). Normal cells located in the wrong tissue degenerate into cancer cells (Biskind and Biskind 1944), whereas neoplastic cells introduced into a blastocyst (Brinster 1974;Mintz and Illmensee 1975;Hochedlinger et al 2004), co-cultured with normal cells (Mizrachi et al 1990), implanted into a normal microenvironment (Mc Cullogh et al 1997) or subjected to differentiating (Missale et al 1998;Bizzarri et al 2003;Sell and Pierce 1994;Wang et al 2002) and embryonic signals (Lee and Herlyn 2006;Lee et al 2005;Cucina et al 2006), either undergo apoptosis or become normal, thereafter contributing to the development of organised ''normal'' bodily structure. Moreover, some preliminary data have shown that differentiating-based treatment responds significantly both in vivo (Yu and Tsai 2001) and in clinical trials (Livraghi et al 2005;Sell 2004).…”

Section: Reversibility Of Cancer Transformationmentioning

confidence: 95%

Beyond the Oncogene Paradigm: Understanding Complexity in Cancerogenesis

et al. 2008

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In the past decades, an enormous amount of precious information has been collected about molecular and genetic characteristics of cancer. This knowledge is mainly based on a reductionistic approach, meanwhile cancer is widely recognized to be a 'system biology disease'. The behavior of complex physiological processes cannot be understood simply by knowing how the parts work in isolation. There is not solely a matter how to integrate all available knowledge in such a way that we can still deal with complexity, but we must be aware that a deeply transformation of the currently accepted oncologic paradigm is urgently needed. We have to think in terms of biological networks: understanding of complex functions may in fact be impossible without taking into consideration influences (rules and constraints) outside of the genome. Systems Biology involves connecting experimental unsupervised multivariate data to mathematical and computational approach than can simulate biologic systems for hypothesis testing or that can account for what it is not known from high-throughput data sets. Metabolomics could establish the requested link between genotype and phenotype, providing informations that ensure an integrated understanding of pathogenic mechanisms and metabolic phenotypes and provide a screening tool for new targeted drug.

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“…PC 12 cells were cultured in DMEM (4.5 g/1 glucose) supplemented with 7.5% FCS and 7.5% horse serum, 2.5 mM Lglutamine, and antibiotics, as previously described (12,13).…”

Section: Cell Culturesmentioning

confidence: 99%

“…Bovine adrenal medullary microvascular endothelial cells (BAME) were grown in Earl's modified Eagle's medium (EMEM, 1 g/1 glucose), supplemented with 10% FCS, 2.5 mM L-glutamine, 30 gg/ml ECGS, 2 Iag/ml heparin, and the antibiotics cocktail described above (12,13).…”

Section: Cell Culturesmentioning

confidence: 99%

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GTSF-2: A new, versatile cell culture medium for diverse normal and transformed mammalian cells

Lelkes

Ramos

Nikolaychik

et al. 1997

In Vitro Cell.Dev.Biol.-Animal

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The aim of this study was to test the versatility of a new basal cell culture medium, GTSF-2. In addition to traditional growth-factors, GTSF-2 contains a blend of three sugars (glucose, galactose, and fructose) at their physiological levels. For these studies, we isolated normal endothelial cells from human, bovine, and rat large blood vessels and microvessels. In addition, GTSF-2 was also tested as a replacement for high-glucose-containing medium for PC12 pheochromocytoma cells and for other, transformed cell lines. The cell growth characteristics were assessed with a novel cell viability and proliferation assay, which is based on the bioreduction of the fluorescent dye, Alamar Blue. After appropriate calibration, the Alamar Blue assay was found to be equivalent to established cell proliferation assays. Alamar Blue offers the advantage that cell proliferation can be measured in the same wells over an extended period of time. For some of the cell types (e.g., endothelial cells isolated from the bovine aorta, the rat adrenal medulla, or the transformed cells), proliferation in unmodified GTSF-2 was equivalent to that in the original culture media. For others cell types (e.g., human umbilical vein endothelial cells and PC12 cells), GTSF-2 proved to be a superior growth medium, when supplemented with simple additives, such as endothelial cell growth supplement (bFGF) or horse serum. Our results suggest that GTSF-2 is a versatile basal medium that will be useful for studying organ-specific differentiation in heterotypic coculture studies.

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PC12 cells differentiate into chromaffin cell-like phenotype in coculture with adrenal medullary endothelial cells.

Abstract: Previously we described specific in vitro interactions between PC12 cells, a cloned, catecholaminesecreting pheochromocytoma cell line derived from the rat adrenal medulla, and bovine adrenal medullary endothelial cells

Cited by 30 publications

References 34 publications

Characterization of an endooligopeptidase A‐like protein in PC12 cells: Activity modulation by cAMP but not by basic fibroblast growth factor

Characterization of an endooligopeptidase A‐like protein in PC12 cells: Activity modulation by cAMP but not by basic fibroblast growth factor

Beyond the Oncogene Paradigm: Understanding Complexity in Cancerogenesis

GTSF-2: A new, versatile cell culture medium for diverse normal and transformed mammalian cells

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