Biology subjects

Lotvall, J.

Publications and source records attributed to Lotvall, J..

3 recordsLinked to original sources

bioRxiv2017

A subgroup of mitochondrial extracellular vesicles discovered in human melanoma tissues are detectable in patient blood

Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations are only beginning to be explored. Since EVs have been implicated in tumor microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Specifically, EVs positive for a combination of the two mitochondrial inner membrane proteins MT-CO2 (mitochondrial genome) and COX6c (nuclear genome) were detected in the plasma of melanoma patients, and in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs, contains active mitochondrial enzymes. Our findings show that tumor tissues are enriched in EVs with mitochondrial proteins and enzymatic activity, and these EVs can be detected in blood.

cancer biology↗

bioRxiv2017

Regulation of mesenchymal stem cell function by TGFβ-1 on mast cell extracellular vesicles -- role of endosomal retention

Extracellular vesicles (EVs) convey biological messages between cells, either by surface-to-surface interaction, or by shuttling of bioactive molecules to a recipient cell cytoplasm. Here we show that EVs released by human primary mast cells or transformed human mast cells (HMC1), carry TGF{beta}-1 on their surface. EV-associated TGF{beta}-1 enhance the migratory activity of human mesenchymal stem cells (MSCs) compared to free TGF{beta}-1, as both knockdown of TGF{beta}, or a TGF{beta}-antibody, attenuate the effect. The MSCs respond by increasing matrix metalloproteinase-2 and -9 (MMP) activity. Further, EVs given to MSCs are retained in the endosomal compartments at a time of biological function, prolonging EV-associated TGF{beta}-1 signaling vs free TGF{beta}-1. When exposed to EVs, MSCs home more toward allergen-exposed lung in a mouse allergen model, resulting in attenuated allergic inflammation. Our results show that mast cell-EVs are decorated with TGFb-1, are retained in endosomes, which influences both MSC phenotype and function.

cell biology↗

bioRxiv2016

Exosomes purified from a single cell type have diverse morphology and composition

Extracellular vesicles (EVs) are produced by all known organisms and have important roles in cell communication and physiology. Exosomes are known in the literature to be small round EVs (40 to 100 nm in diameter) and are commonly purified with a serial ultracentrifugation protocol followed by density gradient floatation. Great morphological diversity has been described before regarding EVs found in body fluids such as blood plasma, breast milk and ejaculate. However, a detailed morphological analysis has never been performed on exosomes purified from a single cell type.\n\nTherefore, the aim of this study was to analyze and quantify via multiple electron microscopy techniques the morphology of exosomes purified from the human mast cell line HMC-1. The results revealed a novel spectrum of diversity in exosomes, which suggests that subpopulations of exosomes with different and specific functions might also exist. Our findings therefore argue that a new and more efficient way of defining exosome subpopulations is necessary. A system was proposed where exosomes were classified into nine different categories according to their size and shape. Three additional morphological features could also be found in exosomes regardless of their classification.\n\nThese findings show that morphological diversity is found among exosomes purified from a single cell line, similarly to what was previously observed for EVs in body fluids. This knowledge can help improving the interpretation of experimental results and widening our general understanding of the biological functions of exosomes.

cell biology↗