The Generation and Characterization of a Cell Line Derived from a Sporadic Renal Angiomyolipoma

Arbiser, Jack L.; Yeung, Raymond S.; Weiss, Sharon W.; Arbiser, Zoya K.; Amin, Mahul B.; Cohen, Cynthia; Frank, David A.; Mahajan, Sudipta; Herron, G. Scott; Yang, Jiwei; Onda, Hiroki; Zhang, H.B.; Bai, Xianhe; Uhlmann, Erik J.; Loehr, Allison; Northrup, Hope; Au, Kit Sing; Davis, Ian J.; Fisher, David E.; Gutmann, David H.

doi:10.1016/s0002-9440(10)61720-8

Cited by 35 publications

(43 citation statements)

References 46 publications

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“…An angiomyolipoma cell line demonstrated variable terminal differentiation into smooth muscle, fat, and melanocytic cells. 22 Ultrastructural studies in cellular neurothekeoma have shown similar phenotypic variation. 19,20 Another point of interest is that the Mitf reactivity of cellular neurothekeomas could potentially cause diagnostic confusion with melanocytic neoplasms.…”

Section: Casementioning

confidence: 93%

Microphthalmia transcription factor and NKI/C3 expression in cellular neurothekeoma

et al. 2004

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While the usual or myxoid-type neurothekeoma has been reasonably well established as being a tumor of neural origin, the cellular neurothekeoma remains in disputed histogenesis. We studied a series of 11 cellular neurothekeomas using paraffin immunoperoxidase staining with microphthalmia transcription factor (Mitf), NKI/C3, and S-100. The majority of the tumors in our series stained with NKI/C3 (9/11) and Mitf (9/11). All failed to stain with S-100. Furthermore, we divided our series of cellular neurothekeomas according to cytomorphology; tumors demonstrating predominantly spindled morphology, predominantly epithelioid morphology, and mixed spindle and epithelioid morphology. The two tumors that failed to stain with NKI/C3 both demonstrated predominantly spindled morphology. One of the tumors that failed to stain with Mitf showed exclusive spindled morphology, while the other showed mixed morphology (spindle and epithelioid). Two of the tumors, which stained strongly with Mitf, however, showed exclusive epithelioid morphology. This current study furthers the concept that cellular neurothekeoma is a tumor of neuroectodermal origin, and further suggests that it may express some component of melanocytic differentiation.

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Section: Casementioning

confidence: 93%

Microphthalmia transcription factor and NKI/C3 expression in cellular neurothekeoma

et al. 2004

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“…Cells derived from renal angiomyolipomas from LAM patients (621-101 TSC2-null cells) were used and maintained in IIA complete medium with 10% (vol/ vol) FBS as previously described (30). Before stimulant treatment, LAM cells were starved overnight in phenol red-, EGF-, and FBS-free IIA complete medium.…”

Section: Methodsmentioning

confidence: 99%

Integration of mTOR and estrogen–ERK2 signaling in lymphangioleiomyomatosis pathogenesis

Ilter

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women associated with the metastasis of tuberin-null cells with hyperactive mammalian target of rapamycin complex 1 (mTORC1) activity. Clinical trials with the mTORC1 inhibitor rapamycin have revealed partial efficacy but are not curative. Pregnancy appears to exacerbate LAM, suggesting that estrogen (E 2 ) may play a role in the unique features of LAM. Using a LAM patient-derived cell line (bearing biallelic Tuberin inactivation), we demonstrate that E 2 stimulates a robust and biphasic activation of ERK2 and transcription of the late response-gene Fra1 associated with epithelialto-mesenchymal transition. In a carefully orchestrated collaboration, activated mTORC1/S6K1 signaling enhances the efficiency of Fra1 translation of Fra1 mRNA transcribed by the E 2 -ERK2 pathway, through the phosphorylation of the S6K1-dependent eukaryotic translation initiation factor 4B. Our results indicate that targeting the E 2 -ERK pathway in combination with the mTORC1 pathway may be an effective combination therapy for LAM.estrogen signaling | mTORC1 signaling | ERK signaling | EMT

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“…However, recent studies have shown that neural crest cells can give rise to smooth muscle cells, as well as melanocytes, and that, in the mouse, multipotent stem cells can be isolated that can differentiate into either melanocytes or smooth muscle cells, depending on the culture condition. These precursor cells express the cell surface markers NG2 and L1 (14)(15)(16)(17)(18). In order to determine whether angiomyolipomas may represent the human equivalent of precursor cells to melanocytes/smooth muscle, we stained angiomyolipoma cells with NG2 and L1 antisera, and found strong expression in angiomyolipoma in vivo, but not in conventional renal cell carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Expression of the Neural Stem Cell Markers NG2 and L1 in Human Angiomyolipoma: Are Angiomyolipomas Neoplasms of Stem Cells?

Lim

Stallcup

Lefkove

et al. 2007

Mol Med

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Angiomyolipomas are benign tumors of the kidney which express phenotypes of smooth muscle, fat, and melanocytes. These tumors appear with increased frequency in the autosomal dominant disorder tuberous sclerosis and are the leading cause of morbidity in adults with tuberous sclerosis. While benign, these tumors are capable of provoking life threatening hemorrhage and replacement of the kidney parenchyma, resulting in renal failure. The histogenesis of these tumors is currently unclear, although currently, we believe these tumors arise from "perivascular epithelioid cells" of which no normal counterpart has been convincingly demonstrated. Recently, stem cell precursors have been recognized that can give rise to smooth muscle and melanocytes. These precursors have been shown to express the neural stem cell marker NG2 and L1. In order to determine whether angiomyolipomas, which exhibit smooth muscle and melanocytic phenotypes, express NG2 and L1, we performed immunocytochemistry on a cell line derived from a human angiomyolipoma, and found that these cells are uniformly positive. Immunohistochemistry of human angiomyolipoma specimens revealed uniform staining of tumor cells, while renal cell carcinomas revealed positivity only of angiogenic vessels. These results support a novel histogenesis of angiomyolipoma as a defect in differentiation of stem cell precursors.

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The Generation and Characterization of a Cell Line Derived from a Sporadic Renal Angiomyolipoma

Cited by 35 publications

References 46 publications

Microphthalmia transcription factor and NKI/C3 expression in cellular neurothekeoma

Microphthalmia transcription factor and NKI/C3 expression in cellular neurothekeoma

Integration of mTOR and estrogen–ERK2 signaling in lymphangioleiomyomatosis pathogenesis

Expression of the Neural Stem Cell Markers NG2 and L1 in Human Angiomyolipoma: Are Angiomyolipomas Neoplasms of Stem Cells?

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