Abstract
Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44high cells produce more organoids with a higher proliferation intensity, as compared to CD44low cells. Interestingly, we detected an increased EV release by CD44high CRC cells. In addition, we found that the miRNA cargos of CD44high and CD44low cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44high cells induced the proliferation and activation of colon fibroblasts more strongly than CD44low cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation.
Highlights
Extracellular vesicles (EV) are membrane-enclosed structures released by virtually all cell types
FFiigguurree11..HHeetteerrooggeenneeoouussexepxprersessisoinonofoCfDC4D44, C4,DC1D331,3a3n,danPdTKP7TiKn7CiRnCCoRrCgaonrogidans.o(iAds).T(hAe)RTNhAe RleNveAl floervethl efoirndthiceaitneddicgaetneeds ginenoersgainnooirdgsa#n1o,i2d,3s a#n1,d2,#34a. nRdN#A4.lRevNeAls wlevereelsnworemrealnizoerdmtaolitzheedHtoPRthTe1HhPoRusTe1kheoeupsienkgegepeninegangdentheeanntdhethneonrmtahleiznedorZmEaBli1zleedveZl EwBa1s tlaekveenl wasa1s. t(aBk)eWn haosle1-.m(oBu)nWt ihmomleu-mnoosutanitniinmgmunostaining for CD44, CD133, and PTK7
We found only one miRNA differentially expressed by CD133high and CD133low organoid-derived EVs and no miRNAs were found to be specific for PTK7high and PTK7low Colorectal cancer (CRC) cell-derived EVs
Summary
Extracellular vesicles (EV) are membrane-enclosed structures released by virtually all cell types. EVs form a heterogeneous population both by size and cellular origin. Since most methods separate EVs based on their size and not on their cellular origin, EVs are often categorized as small (sEV), medium (mEV), and large (lEVs) EVs [3]. EVs carry biologically active molecules, such as miRNAs, lipids, and proteins from the releasing to the target cells, providing a special way of intercellular signal transmission. Since EVs transport their cargo in a protected way in the tissues and body fluids, and molecules specific for the releasing tumor cells are thought to be represented at a high concentration in EVs, they provide a promising tool for early cancer diagnostics. EVs are thought to be involved in intercellular communication, how the presence of different tumor cell subpopulations affects the release, cargo, and functions of EVs is not yet known
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
