LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma: A rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs

Claudia Fiorini, Matteo Brunelli, Luca Cima, Albino Eccher, Luigino Boschiero, Amedeo Carraro, Gianluigi Zaza, Walter Artibani, Antonio B. Porcaro, Giovanni Cacciamani, Umberto Tedeschi, Umberto Montin, Paola Violi, Claudio Ghimenton, Giulia Burato, Roberto Iacovelli, Serena Pedron, Marco Chilosi, Guido Martignoni

Research output: Contribution to journalArticle

Abstract

Background: Targeted drugs to the autophagy processes are emerging in clinical trials. The aim of this work is to assess the magnitude of autophagic expression in renal angiomyolipoma. Methods: Fourteen cases of renal angiomyolipoma were recruited. Anti-LC3B-II and anti-phospho-S6K were detected by Western blot analysis. For immunohistochemical staining, sections were stained with the antibodies LC3B-II and cathepsin-K. LC3B-II was also analyzed by immunofluorescence. We have also carried out electron microscopy analysis on tumor cells. Results: 13 classic and 1 epithelioid renal angiomyolipoma were recruited. The Western-blot LC3B-II analysis shows increasing in protein expression in all cases, however quantitative protein expression ranged from 1 to 15 (mean 5). The autophagosome protein LC3B-I also significantly increased in all tumor extraction. The expression of LC3B-II protein was confirmed in tumoral samples by immunofluorescence. The lysosomal marker cathepsin-K was observed by immunohistochemistry on all tumours. The Western-blot ph-S6K analysis showed significant protein overexpression along all cases after evaluation of the quantitative S6K/Ponceaus ratio. In 6/14 (52%) the expression was high, with a quantitative increase of ≥3 fold induction in 4 angiomyolipoma compared to normal tissue. At electron microscopy, cancer cells evidenced round or oval electron-dense granules associated with membranes and granules with double membrane. Conclusion: Both autophagic LC3B-II and ph-S6K molecules are over-represented in both epithelioid and classic renal angiomyolipoma and a combined use of inhibitors to the autophagic and mTOR processes may be designed in clinical trials, when enrolling patients affected by tumours in tuberous sclerosis or angiomyolipoma at risk of bledding.

Original languageEnglish
Pages (from-to)7020-7029
Number of pages10
JournalInternational Journal of Clinical and Experimental Pathology
Volume9
Issue number7
Publication statusPublished - 2016

Fingerprint

Angiomyolipoma
Kidney
Cathepsin K
Pharmaceutical Preparations
Western Blotting
Neoplasms
Proteins
Fluorescent Antibody Technique
Electron Microscopy
Clinical Trials
Tuberous Sclerosis
Membranes
Autophagy
Immunohistochemistry
Electrons
Staining and Labeling
Antibodies

Keywords

  • Autophagy
  • LC3B
  • MTOR
  • Ph-S6K
  • Renal angiomyolipoma
  • Tuberous sclerosis complex

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma : A rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs. / Fiorini, Claudia; Brunelli, Matteo; Cima, Luca; Eccher, Albino; Boschiero, Luigino; Carraro, Amedeo; Zaza, Gianluigi; Artibani, Walter; Porcaro, Antonio B.; Cacciamani, Giovanni; Tedeschi, Umberto; Montin, Umberto; Violi, Paola; Ghimenton, Claudio; Burato, Giulia; Iacovelli, Roberto; Pedron, Serena; Chilosi, Marco; Martignoni, Guido.

In: International Journal of Clinical and Experimental Pathology, Vol. 9, No. 7, 2016, p. 7020-7029.

Research output: Contribution to journalArticle

Fiorini, C, Brunelli, M, Cima, L, Eccher, A, Boschiero, L, Carraro, A, Zaza, G, Artibani, W, Porcaro, AB, Cacciamani, G, Tedeschi, U, Montin, U, Violi, P, Ghimenton, C, Burato, G, Iacovelli, R, Pedron, S, Chilosi, M & Martignoni, G 2016, 'LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma: A rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs', International Journal of Clinical and Experimental Pathology, vol. 9, no. 7, pp. 7020-7029.
Fiorini, Claudia ; Brunelli, Matteo ; Cima, Luca ; Eccher, Albino ; Boschiero, Luigino ; Carraro, Amedeo ; Zaza, Gianluigi ; Artibani, Walter ; Porcaro, Antonio B. ; Cacciamani, Giovanni ; Tedeschi, Umberto ; Montin, Umberto ; Violi, Paola ; Ghimenton, Claudio ; Burato, Giulia ; Iacovelli, Roberto ; Pedron, Serena ; Chilosi, Marco ; Martignoni, Guido. / LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma : A rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs. In: International Journal of Clinical and Experimental Pathology. 2016 ; Vol. 9, No. 7. pp. 7020-7029.
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abstract = "Background: Targeted drugs to the autophagy processes are emerging in clinical trials. The aim of this work is to assess the magnitude of autophagic expression in renal angiomyolipoma. Methods: Fourteen cases of renal angiomyolipoma were recruited. Anti-LC3B-II and anti-phospho-S6K were detected by Western blot analysis. For immunohistochemical staining, sections were stained with the antibodies LC3B-II and cathepsin-K. LC3B-II was also analyzed by immunofluorescence. We have also carried out electron microscopy analysis on tumor cells. Results: 13 classic and 1 epithelioid renal angiomyolipoma were recruited. The Western-blot LC3B-II analysis shows increasing in protein expression in all cases, however quantitative protein expression ranged from 1 to 15 (mean 5). The autophagosome protein LC3B-I also significantly increased in all tumor extraction. The expression of LC3B-II protein was confirmed in tumoral samples by immunofluorescence. The lysosomal marker cathepsin-K was observed by immunohistochemistry on all tumours. The Western-blot ph-S6K analysis showed significant protein overexpression along all cases after evaluation of the quantitative S6K/Ponceaus ratio. In 6/14 (52{\%}) the expression was high, with a quantitative increase of ≥3 fold induction in 4 angiomyolipoma compared to normal tissue. At electron microscopy, cancer cells evidenced round or oval electron-dense granules associated with membranes and granules with double membrane. Conclusion: Both autophagic LC3B-II and ph-S6K molecules are over-represented in both epithelioid and classic renal angiomyolipoma and a combined use of inhibitors to the autophagic and mTOR processes may be designed in clinical trials, when enrolling patients affected by tumours in tuberous sclerosis or angiomyolipoma at risk of bledding.",
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T1 - LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma

T2 - A rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs

AU - Fiorini, Claudia

AU - Brunelli, Matteo

AU - Cima, Luca

AU - Eccher, Albino

AU - Boschiero, Luigino

AU - Carraro, Amedeo

AU - Zaza, Gianluigi

AU - Artibani, Walter

AU - Porcaro, Antonio B.

AU - Cacciamani, Giovanni

AU - Tedeschi, Umberto

AU - Montin, Umberto

AU - Violi, Paola

AU - Ghimenton, Claudio

AU - Burato, Giulia

AU - Iacovelli, Roberto

AU - Pedron, Serena

AU - Chilosi, Marco

AU - Martignoni, Guido

PY - 2016

Y1 - 2016

N2 - Background: Targeted drugs to the autophagy processes are emerging in clinical trials. The aim of this work is to assess the magnitude of autophagic expression in renal angiomyolipoma. Methods: Fourteen cases of renal angiomyolipoma were recruited. Anti-LC3B-II and anti-phospho-S6K were detected by Western blot analysis. For immunohistochemical staining, sections were stained with the antibodies LC3B-II and cathepsin-K. LC3B-II was also analyzed by immunofluorescence. We have also carried out electron microscopy analysis on tumor cells. Results: 13 classic and 1 epithelioid renal angiomyolipoma were recruited. The Western-blot LC3B-II analysis shows increasing in protein expression in all cases, however quantitative protein expression ranged from 1 to 15 (mean 5). The autophagosome protein LC3B-I also significantly increased in all tumor extraction. The expression of LC3B-II protein was confirmed in tumoral samples by immunofluorescence. The lysosomal marker cathepsin-K was observed by immunohistochemistry on all tumours. The Western-blot ph-S6K analysis showed significant protein overexpression along all cases after evaluation of the quantitative S6K/Ponceaus ratio. In 6/14 (52%) the expression was high, with a quantitative increase of ≥3 fold induction in 4 angiomyolipoma compared to normal tissue. At electron microscopy, cancer cells evidenced round or oval electron-dense granules associated with membranes and granules with double membrane. Conclusion: Both autophagic LC3B-II and ph-S6K molecules are over-represented in both epithelioid and classic renal angiomyolipoma and a combined use of inhibitors to the autophagic and mTOR processes may be designed in clinical trials, when enrolling patients affected by tumours in tuberous sclerosis or angiomyolipoma at risk of bledding.

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KW - MTOR

KW - Ph-S6K

KW - Renal angiomyolipoma

KW - Tuberous sclerosis complex

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