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@MASTERSTHESIS{DaSilvaAzevedo:177453,
      author       = {J. Da Silva Azevedo$^*$},
      title        = {{I}nterconnection between cancer derived small
                      extracellular vesicles and lipid droplets},
      school       = {University of Applied Sciences Mannheim},
      type         = {Bachelorarbeit},
      reportid     = {DKFZ-2021-02545},
      year         = {2021},
      note         = {Corresponding author J. Seco; Bachelorarbeit, University of
                      Applied Sciences Mannheim, 2021},
      abstract     = {Small extracellular vesicles (sEVs) are nanovesicles
                      enclosed by a phospholipid bilayer membrane and are produced
                      by both healthy and malignant cells. sEVs are responsible
                      for cell-to-cell communication and have been described as
                      performing a variety of functions that alter the
                      physiological or pathological state of the recipient cells.
                      They can enhance tumor development and progression by
                      promoting metastasis and angiogenesis via regulation of the
                      tumoral microenvironment [1]. All these factors have led to
                      the growing interest in discovering potential future
                      therapeutic sEV-based approaches, such as drug delivery
                      vehicles. Increasing evidence indicates that lipid
                      metabolism influences sEV biological activities such as
                      biosyn-thesis and interactions with recipient cells. This is
                      likely related to the fact that lipids that are stored and
                      released from lipid droplets (LDs) are key components of the
                      plasma membrane, which can reprogram their fluidity
                      contributing to an optimal environment for the exchange of
                      genetic material between cells. The aim of this project was
                      to investigate the correlation be-tween the release of
                      tumor-derived sEVs and the biogenesis of lipid droplets. In
                      order to study this connection, several types of experiments
                      were used in this bachelor thesis. Previous studies have
                      shown evidence that tumor acidity and sEV biogenesis
                      represent common can-cer features [2] along with the
                      confirmation that X-ray activates sEV biogenesis and
                      secretion [3]. Therefore, this project was focused to
                      investigate how the stimulation by these conditions affected
                      the biogenesis of sEVs and lipid droplets in cancer cell
                      lines isolated from the breast (MCF7) and lung (H460)
                      tumors. To this purpose, the two cell lines were cultured in
                      either a neutral pH (7.4) or an acidic pH (6.5) typical of
                      tumor environment [4]. Additionally, cell lines were
                      irradiated with 6 Gy for the radiation experiment. The
                      number of released sEVs was measured by fluorometric protein
                      quantification and nanoparticle tracking analysis (NTA). The
                      expression of sEV protein markers was examined by Western
                      blotting. Moreover, sEVs were characterized by electron
                      microscopy. The produced LD number per cell was obtained
                      through fluorescent confocal microscopy. Furthermore, two
                      tumor-derived colon cell lines, HT29 and LoVo, were directly
                      compared for the biogenesis of sEVs and lipid droplets.
                      Previ-ous studies showed that LoVo has small amounts of LDs
                      within cells in comparison to HT29 [5]. For this study, Lovo
                      was perceived as the control and compared to HT29 which has
                      a natural higher LD accumulation. The experimental setup was
                      essentially the same with the exception that cells were not
                      exposed to treatment. The results showed that pH 6.5 and 6
                      Gy induced a remarkable increase in sEVs and LD production,
                      and the control groups had the opposite outcome for all
                      cancer cell lines. The cell lines LoVo and HT29, which were
                      not in-duced by artificial conditioning, showed an
                      experimental model which reflects natural settings. The
                      outcome confirmed the hypothesis that there is an
                      interconnection in the biogenesis pathway between the two
                      cell organelles, but further in-depth research is needed to
                      uncover the mechanistic processes underlying this potential
                      connection.},
      cin          = {E041},
      cid          = {I:(DE-He78)E041-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)2},
      url          = {https://inrepo02.dkfz.de/record/177453},
}