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Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer

  1. Wah Chiua,b,1
  1. aGraduate Program in Structural and Computational Biology and Molecular Biophysics, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030;
  2. bNational Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030;
  3. cDepartment of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
  4. dDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030;
  5. eDepartment of Medicine, Baylor College of Medicine, Michael E. DeBakey Veterans Affair Medical Center, Houston, TX 77030;
  6. fCenter for Translational Research on Inflammation, Michael E. DeBakey Veterans Affair Medical Center, Houston, TX 77030;
  7. gPuget Sound Blood Center, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98104;
  8. hDivision of Hematology, Department of Medicine, School of Medicine, University of Washington, Seattle, WA 98104;
  9. iDepartment of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;
  10. jCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030

  1. Contributed by Wah Chiu, September 30, 2015 (sent for review March 1, 2015; reviewed by Peter Frederik, Jun Liu, Kunle Odunsi, and David W. Scott)

Significance

Platelets are known to be both numerically and functionally altered in some patients with cancer. However, structural differences in the platelets from these patients have not been studied. Here we use electron cryotomography to reveal that, compared with control donors, the microtubule system and the mitochondria of platelets from patients diagnosed with ovarian cancer are significantly different. This finding suggests the potential of electron cryotomography as a technology to detect structural biomarkers of diseases affecting platelets.

Abstract

Thrombocytosis and platelet hyperreactivity are known to be associated with malignancy; however, there have been no ultrastructure studies of platelets from patients with ovarian cancer. Here, we used electron cryotomography (cryo-ET) to examine frozen-hydrated platelets from patients with invasive ovarian cancer (n = 12) and control subjects either with benign adnexal mass (n = 5) or free from disease (n = 6). Qualitative inspections of the tomograms indicate significant morphological differences between the cancer and control platelets, including disruption of the microtubule marginal band. Quantitative analysis of subcellular features in 120 platelet electron tomograms from these two groups showed statistically significant differences in mitochondria, as well as microtubules. These structural variations in the platelets from the patients with cancer may be correlated with the altered platelet functions associated with malignancy. Cryo-ET of platelets shows potential as a noninvasive biomarker technology for ovarian cancer and other platelet-related diseases.

Footnotes

  • ↵1To whom correspondence may be addressed. Email: wah{at}bcm.edu or asood{at}mdanderson.org.

  • Author contributions: M.F.S., J.-F.D., A.K.S., and W.C. designed research; R.W., R.L.S., V.A.-K., and M.F.S. performed research; R.W., R.L.S., A.M.N., K.V.V., and M.F.S. contributed new reagents/analytic tools; R.W., J.T.K., R.H.R., M.F.S., J.-F.D., A.K.S., and W.C. analyzed data; and R.W., J.T.K., V.A.-K., M.F.S., J.-F.D., A.K.S., and W.C. wrote the paper.

  • Reviewers: P.F., Maastricht University; J.L., University of Texas Medical School at Houston; K.O., Roswell Park Cancer Institute; and D.W.S., Rice University.

  • The authors declare no conflict of interest.

  • Data deposition: Representative tomograms of platelets in three different pathophysiological states reported in this paper have been deposited in the EMDataBank, www.emdatabank.org/ (accession nos. EMD-6471, EMD-6472, and EMD-6473).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1518628112/-/DCSupplemental.

Freely available online through the PNAS open access option.

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