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. 2011 Sep 29;118(13):3680-3.
doi: 10.1182/blood-2011-03-344408. Epub 2011 Aug 10.

Blood platelets contain tumor-derived RNA biomarkers

R Jonas A Nilsson  1 , Leonora Balaj, Esther Hulleman, Sjoerd van Rijn, D Michiel Pegtel, Maudy Walraven, Anders Widmark, Winald R Gerritsen, Henk M Verheul, W Peter Vandertop, David P Noske, Johan Skog, Thomas Würdinger
Affiliations

Blood platelets contain tumor-derived RNA biomarkers

R Jonas A Nilsson et al. Blood. .

Abstract

Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Uptake of tumor-derived RNA in platelets. (A) U87 glioma-derived microvesicles were labeled with PKH67 green fluorescent dye and incubated with isolated platelets. After 15, 30, 45, and 60 minutes of incubation in the presence and absence of microvesicles, the platelets were washed and subjected to FACS analysis of PKH67 fluorescence. (B) Platelets were incubated with PKH67-labeled microvesicles (MV) from glioma or prostate cancer (PCa) patients, stained with Texas-red wheat germ agglutinin, and analyzed by confocal microscopy for PKH67-labeled microvesicle uptake. Merged images and size bars are shown. (C) RNA was isolated from RNAse-treated platelets after incubation with U87 glioma-derived microvesicles under different conditions. RT-PCR was performed to detect EGFRvIII RNA. MV/MV-EGFRvIII indicates microvesicles isolated from U87/U87-EGFRvIII cells. (D) Mice were implanted with U87-Fluc-EGFRvIII cells or no cells and imaged after 2 weeks. Shown are representative bioluminescence images and corresponding EGFRvIII RT-PCR on mouse platelets. (E) RNA was isolated from platelets from 12 healthy control subjects and 26 glioma patients (only 18 patients shown here) and subjected to RT-PCR analysis. Corresponding glioma tissue biopsies served as control. Platelet activation and heterogeneous EGFRvIII tissue distribution may have caused the possible false-negative signals. PC indicates U87-EGFRvIII RNA; NC, H2O; and nd, not determined. *Positive signal. (F) RNA was isolated from platelets from healthy control subjects (n = 10) and prostate cancer patients (n = 12) and subjected to PCA3 and GAPDH RT-PCR analysis.
Figure 2
Figure 2
Glioma-associated gene expression signature. (A) Platelet RNA from glioma patients and healthy control subjects was subjected to gene-expression arrays. SAM analysis was used to determine significantly expressed genes. A heatmap of the top-30 up-regulated RNAs is shown. (B) Individual expression levels for the top-10 RNAs. Dashed line indicates background (BG).
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