Skip to main content

Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma.

Publication ,  Journal Article
Hemachandra, LPMP; Shin, D-H; Dier, U; Iuliano, JN; Engelberth, SA; Uusitalo, LM; Murphy, SK; Hempel, N
Published in: Cancer Res
November 15, 2015

Epithelial ovarian cancer (EOC) is the fourth leading cause of death due to cancer in women and comprises distinct histologic subtypes, which vary widely in their genetic profiles and tissues of origin. It is therefore imperative to understand the etiology of these distinct diseases. Ovarian clear cell carcinoma (OCCC), a very aggressive subtype, comprises >10% of EOCs. In the present study, we show that mitochondrial superoxide dismutase (Sod2) is highly expressed in OCCC compared with other EOC subtypes. Sod2 is an antioxidant enzyme that converts highly reactive superoxide (O2 (•-)) to hydrogen peroxide (H2O2) and oxygen (O2), and our data demonstrate that Sod2 is protumorigenic and prometastatic in OCCC. Inhibiting Sod2 expression reduces OCCC ES-2 cell tumor growth and metastasis in a chorioallantoic membrane (CAM) model. Similarly, cell proliferation, migration, spheroid attachment and outgrowth on collagen, and Akt phosphorylation are significantly decreased with reduced expression of Sod2. Mechanistically, we show that Sod2 has a dual function in supporting OCCC tumorigenicity and metastatic spread. First, Sod2 maintains highly functional mitochondria, by scavenging O2 (•-), to support the high metabolic activity of OCCC. Second, Sod2 alters the steady-state ROS balance to drive H2O2-mediated migration. While this higher steady-state H2O2 drives prometastatic behavior, it also presents a doubled-edged sword for OCCC, as it pushed the intracellular H2O2 threshold to enable more rapid killing by exogenous sources of H2O2. Understanding the complex interaction of antioxidants and ROS may provide novel therapeutic strategies to pursue for the treatment of this histologic EOC subtype.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

November 15, 2015

Volume

75

Issue

22

Start / End Page

4973 / 4984

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Reactive Oxygen Species
  • RNA, Small Interfering
  • Oxidative Stress
  • Oxidation-Reduction
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Invasiveness
  • Immunoblotting
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Hemachandra, L. P. M. P., Shin, D.-H., Dier, U., Iuliano, J. N., Engelberth, S. A., Uusitalo, L. M., … Hempel, N. (2015). Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma. Cancer Res, 75(22), 4973–4984. https://doi.org/10.1158/0008-5472.CAN-14-3799
Hemachandra, LP Madhubhani P., Dong-Hui Shin, Usawadee Dier, James N. Iuliano, Sarah A. Engelberth, Larissa M. Uusitalo, Susan K. Murphy, and Nadine Hempel. “Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma.Cancer Res 75, no. 22 (November 15, 2015): 4973–84. https://doi.org/10.1158/0008-5472.CAN-14-3799.
Hemachandra LPMP, Shin D-H, Dier U, Iuliano JN, Engelberth SA, Uusitalo LM, et al. Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma. Cancer Res. 2015 Nov 15;75(22):4973–84.
Hemachandra, LP Madhubhani P., et al. “Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma.Cancer Res, vol. 75, no. 22, Nov. 2015, pp. 4973–84. Pubmed, doi:10.1158/0008-5472.CAN-14-3799.
Hemachandra LPMP, Shin D-H, Dier U, Iuliano JN, Engelberth SA, Uusitalo LM, Murphy SK, Hempel N. Mitochondrial Superoxide Dismutase Has a Protumorigenic Role in Ovarian Clear Cell Carcinoma. Cancer Res. 2015 Nov 15;75(22):4973–4984.

Published In

Cancer Res

DOI

EISSN

1538-7445

Publication Date

November 15, 2015

Volume

75

Issue

22

Start / End Page

4973 / 4984

Location

United States

Related Subject Headings

  • Superoxide Dismutase
  • Reactive Oxygen Species
  • RNA, Small Interfering
  • Oxidative Stress
  • Oxidation-Reduction
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Neoplasm Invasiveness
  • Immunoblotting