Extracellular vesicles (EVs) carry genetic and biological cargo between cells and are present in body fluids. Their contents could include valuable cancer biomarkers, such as microRNAs (miRNAs), but there are no well-defined methods for differentiating EVs derived from cancer versus normal cells. Researchers led by Honami Naora, Ph.D., at MD Anderson Cancer Center identified that the glycoprotein CD147 is expressed on EVs that lack tetraspanins, the most commonly used surface markers of EVs. The study showed a higher prevalence of CD147-positive EVs, but not tetraspanin-positive EVs, in patients with renal and ovarian cancers compared to healthy individuals. The researchers discovered that CD147-positive EVs are derived predominantly from cancer cells and have substantially higher miRNA content than tetraspanin-positive EVs. Additionally, miRNAs isolated using CD147 immunocapture closely reflect tumor miRNA signatures, highlighting a viable approach for detecting cancer-derived miRNA in multiple disease sites.
Biogenesis of CD147+ and CD98+ EVs is distinct from that of tetraspanin+ EVs
(a) Subcellular localization of CD63, CD81, CD9, CD147 and CD98 detected by immunofluorescence staining in HeLa cells and visualized by confocal microscopy. Nuclei were visualized by staining with DAPI. Enlarged insets show the presence of CD147 and CD98 in regions of the plasma membrane that bleb outwardly or have pinched off (denoted by arrows). (b, c) 293T cells that express the tetracycline repressor protein were stably transfected with tetracycline-regulated HGS shRNA or TSG101 shRNA, or with TRIPZ vector. In (b), levels of HGS, TSG101 and the indicated surface markers detected by immunoblot in equivalent amounts of cell lysates (20 μg) of untreated and doxycycline-treated cells. In (c), numbers of CD63+, CD81+, CD9+, CD147+ and CD98+ EVs produced by equivalent numbers of 293T cells (∼5 × 106) without and following doxycycline-induced knockdown of HGS and TSG101. Mean ± SD of n = 5 independent experiments are shown. ns, not significant, ****P < 0.0001, by unpaired two-tailed Student’s t-test in c.
Source – Eurekalert