Vesicles In Tissues Research Articles

Chapter Five - Hyaluronan-Coated Extracellular Vesicles—A Novel Link Between Hyaluronan and Cancer

The synthesis of hyaluronan (HA) on the plasma membrane is a unique and still partly mysterious way of macromolecular biosynthesis. HA forms pericellular coats around many cell types and accumulates in the extracellular matrix (ECM) of growing and renewing tissues. It is secreted to high concentrations in body fluids with antifriction properties like pleural, peritoneal, and synovial fluids, but is also detectable in plasma, saliva, and urine. In pathological states, like cancer and inflammation, the amount of HA is increased around cells, in the ECM, and in the body fluids. HA is an indicator of poor prognosis for cancer patients and creates a favorable environment for cellular growth and motility. The recent finding that HA-coated extracellular vesicles act both as a product of HA synthase activity and as special vehicles for HA, and perhaps carry signals important for malignant growth, provides a novel link between HA and cancer. HA could be carried on the surface of these vesicles in tissues and body fluids, creating beneficial environments by itself, or by associated molecules, for the invasion and metastasis of cancer cells. The HA-coated plasma membrane protrusions and vesicles shed from them are potential biomarkers in cancer and other HA-associated disease states.

A method to assess the migration properties of cell-derived microparticles within a living tissue

BackgroundCells undergoing activation or apoptosis exhibit plasma membrane changes, leading to the formation of shed vesicles (microparticles, MP). Although their effects on recipient cells in vitro, and their ability to support inflammatory or thrombotic events in the circulation have been studied, the spreading of such vesicles in tissues is still elusive. Our aim was to set up a method to examine the behavior of these vesicles in vivo. MethodsWe examined the persistence of green-fluorescent microparticles (fMP), prepared after Ca2+ ionophore activation (iono-fMP) or apoptogenic treatment (eto-fMP) of human Jurkat T lymphoblastic or non-hematopoietic embryonic kidney (HEK) cell lines, following injection in zebrafish embryos 2h after egg fertilization. ResultsOne hour post-injection, iono-fMP issued from both cell types formed a fluorescent dispersal in the intercellular space of embryos. In contrast, eto-fMP or MP deprived of sialic acid at their membrane, gathered together at the site of injection. ConclusionsWe propose a method characterizing the abilities of MP to spread in the intercellular space. We showed that MP produced by apoptosis of T cells and those deprived of sialic acid at their membrane do not diffuse within the living cells. On the contrary, MP shed upon calcium induced activation of T and HEK cells, diffuse at a distance and spread in the intercellular space. General SignificanceThe fate of injected MP relies on the type of induction rather than the cell species and results provide a model to test the ability of vesicles to interact locally or to spread outside of the site of production.

Stability of lipid vesicles in tissues of the mouse: a gamma-ray perturbed angular correlation study.

The rate of phospholipid vesicle disruption in specific tissues of the mouse was followed by gamma-ray perturbed angular correlation (PAC) spectroscopy. In these studies, high levels of 111In-nitrilotriacetic acid complex are contained in unilamellar vesicles consisting of distearoyl phosphatidylcholine, cholesterol, and small amounts of other lipids which modify the surface properties. The PAC technique monitors the extent of vesicle breakup by measuring a time-integrated perturbation factor, less than G22 (infinity) greater than. As the vesicles are broken open in vivo, the released 111In3+ ions quickly bind to macromolecules and the less than G22 (infinity) greater than value decreases substantially. After administration of vesicles by various routes (intravenous, intraperitoneal, subcutaneous, and oral), the radioactivity and less than G22 (infinity) greater than values were determined for several tissues at intervals up to 24 hr. We conclude from these data that (i) the PAC technique in conjunction with standard gamma counting methods provides unique information on the condition and location of vesicles in specific tissues, (ii) significant differences in vesicle integrity are found in various tissues, and (iii) both the means of administration and the presence of surface charge affect the vesicle stability and distribution. The carbohydrate analogues of cholesterol affect vesicle stability but not distribution.

Membranes of mammary gland: XV. 5-Thio- d-glucose decreases lactose content and inhibits secretory vesicle maturation in lactating rat mammary gland

Short-term administration of the glucose analog 5-thio- d-glucose to primiparous lactating rats reduced mammary tissue lactose concentrations to half of control levels. Treatment with colchicine alone caused slight reductions in mammary tissue lactose content. These treatments did not alter the morphology or degree of development of rough endoplasmic reticulum or Golgi apparatus, but did cause alterations in secretory vesicles. In mammary tissue from untreated lactating animals, large, swollen secretory vesicles were abundant in apical regions of epithelial cells. After thioglucose administration secretory vesicles in the apical cytoplasm were smaller and were more densely packed with contents. While administration of colchicine alone caused accumulation of large numbers of nearly fully swollen vesicles, treatment with both colchicine and thioglucose induced accumulation of smaller, less fully developed secretory vesicles which contained morphologically recognizable casein micelles. Mammary tissue from late gestation rats was low in lactose; vesicles in this tissue resembled secretory vesicles in tissue from rats treated with thioglucose in that they were small and densely packed. These observations suggest that lactose, an osmoregulator in mammary gland, is transferred from Golgi apparatus to the apical cell surface within secretory vesicles. Lactose appears to be important for secretory vesicle maturation in mammary epithelial cells.