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Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.

Publication ,  Journal Article
Zhang, H; Wei, Q; Tsushima, H; Puviindran, V; Tang, YJ; Pathmanapan, S; Poon, R; Ramu, E; Al-Jazrawe, M; Wunder, J; Alman, BA
Published in: JCI Insight
April 30, 2019

Enchondroma and chondrosarcoma are the most common benign and malignant cartilaginous neoplasms. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are present in the majority of these tumors. We performed RNA-seq analysis on chondrocytes from Col2a1Cre;Idh1LSL/+ animals and found that genes implied in cholesterol synthesis pathway were significantly upregulated in the mutant chondrocytes. We examined the phenotypic effect of inhibiting intracellular cholesterol biosynthesis on enchondroma formation by conditionally deleting SCAP (sterol regulatory element-binding protein cleavage-activating protein), a protein activating intracellular cholesterol synthesis, in IDH1 mutant mice. We found fewer enchondromas in animals lacking SCAP. Furthermore, in chondrosarcomas, pharmacological inhibition of intracellular cholesterol synthesis significantly reduced chondrosarcoma cell viability in vitro and suppressed tumor growth in vivo. Taken together, these data suggest that intracellular cholesterol synthesis is a potential therapeutic target for enchondromas and chondrosarcomas.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

April 30, 2019

Volume

5

Issue

11

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Mice, Knockout
  • Mice
  • Lovastatin
  • Isocitrate Dehydrogenase
  • Genetic Predisposition to Disease
  • Disease Models, Animal
  • Chondrosarcoma
  • Chondroma
  • Chondrocytes
 

Citation

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Zhang, H., Wei, Q., Tsushima, H., Puviindran, V., Tang, Y. J., Pathmanapan, S., … Alman, B. A. (2019). Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma. JCI Insight, 5(11). https://doi.org/10.1172/jci.insight.127232
Zhang, Hongyuan, Qingxia Wei, Hidetoshi Tsushima, Vijitha Puviindran, Yuning J. Tang, Sinthu Pathmanapan, Raymond Poon, et al. “Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.JCI Insight 5, no. 11 (April 30, 2019). https://doi.org/10.1172/jci.insight.127232.
Zhang H, Wei Q, Tsushima H, Puviindran V, Tang YJ, Pathmanapan S, et al. Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma. JCI Insight. 2019 Apr 30;5(11).
Zhang, Hongyuan, et al. “Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma.JCI Insight, vol. 5, no. 11, Apr. 2019. Pubmed, doi:10.1172/jci.insight.127232.
Zhang H, Wei Q, Tsushima H, Puviindran V, Tang YJ, Pathmanapan S, Poon R, Ramu E, Al-Jazrawe M, Wunder J, Alman BA. Intracellular cholesterol biosynthesis in enchondroma and chondrosarcoma. JCI Insight. 2019 Apr 30;5(11).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

April 30, 2019

Volume

5

Issue

11

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Mice, Knockout
  • Mice
  • Lovastatin
  • Isocitrate Dehydrogenase
  • Genetic Predisposition to Disease
  • Disease Models, Animal
  • Chondrosarcoma
  • Chondroma
  • Chondrocytes