Increased vesiculability of platelets in 24 patients with gastrointestinal cancer

  • Eva Ogorevc Laboratorij za biofiziko Fakulteta za elektrotehniko Univerza v Ljubljani Tržaška 25 1000 Ljubljana
  • Apolonija Bedina-Zavec Laboratorij za biosintezo in biotransformacijo Kemijski inštitut Hajdrihova 19 1000 Ljubljana
  • Roman Štukelj Zdravstvena fakulteta Univerza v Ljubljani Zdravstvena 5 1000 Ljubljana
  • Vid Šuštar Laboratorij za klinično biofiziko Katedra za ortopedijo Medicinska fakulteta Univerza v Ljubljani Zaloška 9 1000 Ljubljana
  • Rado Janša Klinični oddelek za gastroenterologijo Univerzitetni klinični center Ljubljana Japljeva 2 1000 Ljubljana
Keywords: cell-derived microparticles, gastrointestinal neoplasms, neoplasm metastasis, thrombosis, cell membrane

Abstract

Background: Cell nanovesicles (NVs) are small (mostly nano-sized) membrane-enclosed cell fragments that are pinched off from the cell due to rearrangement of its constituents. We have determined concentration of NVs in isolates from blood in populations of patients with gastrointestinal cancer, patients with other gastrointestinal diseases and in healthy subjects. To study whether NVs derive from platelets, we considered correlations between the concentration of platelets in blood and the concentration of NVs in isolates from blood, and between vesiculability of platelets and concentration of NVs in isolates from blood.

Methods: Blood samples were collected from 24 patients with gastrointestinal cancer, 28 patients with other gastrointestinal diseases and 49 healthy volunteers. NVs were isolated by centrifugation and washing of samples and counted by flow cytometry. Isolation was performed at 37 °C. Platelets were counted by impedance method. Populations were compared by methods of descriptive statistics.

Results: In patients with gastrointestinal cancer the concentration of NVs in isolates from blood was considerably (44 %) and statistically significantly (p = 0.0005) higher than in healthy subjects and considerably (34 %) and statsitically significantly (p = 0.025) higher than in patients with other gastrointestinal diseases. There was no statistically significant correlation between the concentration of NVs in isolates from blood and the concentration of platelets in blood (r = 0.1820, p = 0.0801). We found a statistically significant positive correlation between vesiculability of platelets and concentration of NVs in isolates from blood (r = 0.5690, p = 0,0000).

Conclusions: Fragility of platelet membrane in blood is increased in patients with gastrointestinal cancer.

Downloads

Download data is not yet available.

References

Kralj-Iglič V, Iglič A, Hagerstrand H, Bobrowska-Hagerstrand M, Hypothesis on nanostructures of cell and phospholipid membranes as cell infrastructure. Med Razgl 2005; 44(2): 155–69.

Kralj-Iglič V, Batista U, Hagerstrand H, Iglič A, Majhenc J, Sok M. On mechanisms of cell plasma membrane vesiculation. Radiol Oncol 1998; 32: 119–23.

Kralj-Iglič V, Iglič A, Hagerstrand H, Peterlin P. Stable tubular microexovesicles of the erythrocyte membrane induced by dimeric amphiphiles. Phys Rev E 2000; 61: 4230–4.

Šuštar V, Bedina-Zavec A, Štukelj R, Frank M, Bobojević G, Janša R, et al. Nanoparticles isolated from blood – a reflection of vesiculability of blood cells during the isolation process. Int J Nanomed; 2011; 6: 2737–48.

Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 2006; 20(9): 1487–95.

Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int 2010; 78(9): 838–48.

Pisetsky DS. Microparticles as biomarkers in autoimmunity: from dust bin to center stage. Arthritis Res Ther 2009; 11: 135

Schara K, Janša V, Šuštar V, Dolinar D, Pavlič JI, Lokar M, et al. Mechanisms for the formation of membranous nanostructures in cell-to-cell communication. Cell Mol Biol Lett 2009; 14: 636–56.

Müller I, Klocke A, Alex M, Kotzsch, M, Luther T, Morgenstern E, et al. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J 2000; 17: 476–8.

Lee TH, D’Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J. Microvesicles as mediators of intercellular communication in cancer–the emerging science of cellular ‘debris’. Semin Immunopathol 2011; 33(5): 455–67.

Ginestra A, La Placa MD, Saladino F, Cassara D, Nagase H, Vittorelli ML. The amount and proteolytic content of vesicles shed by human cancer cell lines correlates with their in vitro invasiveness. Anticancer Res 1998; 18(5A): 3433–7.

Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008; 10(12): 1470-U209.

Abid Hussein MN, Boing AN, Sturk A, Hau CM, Nieuwland R. Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb Haemost 2007; 98 (5): 1096–107.

Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 2005; 113 (5): 752–60.

Safaei R, Larson BJ, Cheng TC, Gibson MA, Otani S, Naerdemann W, Howell SB. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol Cancer Ther 2005; 4 (10): 1595–604.

Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR. Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 2003; 63 (15): 4331–7.

Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 2006; 66 (18): 9290–8.

Kralj-Iglič V. Stability of membranous nanostructures: a possible key mechanism in cancer progression. Int J Nanomed 2012; 7: 3579–96.

Atanasijevič-Kunc M, Drinovec J, Guštin B, Mrhar A. Simulation analysis of economic burden in hypertension and myocardial infarction treatment with beta blockers. Slov Med J 2012; 81 (2): 105–18.

Diamant M, Nieuwland R, Pablo RF, Sturk A, Smit JW, Radder JK. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 2002; 106: 2442–7.

Junkar I, Šuštar V, Frank M, Janša V, Bedina-Zavec A, Rozman B, et al. Blood and synovial microparticles as revealed by atomic force and scanning electron microscope. Open Autoimmun J 2009; 1:e50-e58.

Mrvar-Brečko A, Šuštar V, Janša V, Štukelj R, Janša R, Mujagić E, et al. Isolated microvesicles from peripheral blood and body fluids as observed by scanning electron microscope. Blood Cell Mol Dis 2010; 44: 307–12.

Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 2004; 101 (36): 13368–73.

Gonzales P, Pisitkun T, Knepper MA. Urinary exosomes: is there a future? Nephrol Dial Transplant 2008; 23 (6): 1799–801.

Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA. Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res 2004; 64 (19): 7045–9.

Skriner K, Adolph K, Jungblut PR, Burmester GR. Association of citrullinated proteins with synovial exosomes. Arthritis Rheum 2006; 54 (12): 3809–14.

Bard MP, Hegmans JP, Hemmes A, Luider TM, Willemsen R, Severijnen LA, et al. Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am J Respir Cell Mol Biol 2004; 31(1): 114–21.

Sullivan R, Saez F, Girouard J, Frenette G. Role of exosomes in sperm maturation during the transit along the male reproductive tract. Blood Cells Mol Dis 2005; 35(1): 1–10.

Admyre C, Johansson SM, Qazi KR, Filen JJ, Lahesmaa R, Norman M, et al. Exosomes with immune modulatory features are present in human breast milk. J Immunol 2007; 179 (3): 1969–78.

Taylor DD, Akyol S, Gercel-Taylor C. Pregnancy-associated exosomes and their modulation of T cell signaling. J Immunol 2006; 176 (3): 1534–42.

Asea A, Jean-Pierre C, Kaur P, Rao P, Linhares IM, Skupski D, Witkin SS. Heat shock protein-containing exosomes in mid-trimester amniotic fluids. J Reprod Immunol 2008; 79 (1): 12–17.

Perkumas KM, Hoffman EA, McKay BS, Allingham RR, Stamer WD. Myocilin-associated exosomes in human ocular samples. Exp Eye Res 2007; 84 (1): 209–12.

Ogawa Y, Kanai-Azuma M, Akimoto Y, Kawakami H, Yanoshita R. Exosome-like vesicles with dipeptidyl peptidase IV in human saliva. Biol Pharm Bull 2008; 31(6): 1059–62.

Gruden K, Hren M, Herman A, Blejec A, Albrecht T, Selbig J, et al. A »crossomics« study analysing variability of different components in peripheral blood of health caucasoid individuals. PloS ONE 2012; 7(1): e28761.

Janša R, Šuštar V, Frank M, Sušanj P, Bešter J, Manček-Keber M, et al. Number of microvesicles in peripheral blood and ability of plasma to induce adhesion between phospholipid membranes in 19 patients with gastrointestinal diseases. Blood Cells Mol Dis 2008; 41(1): 124–32.

Kim HK, Song KS, Park YS, Kang YH, Lee YJ, Lee KR, et al. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 2003; 39(2): 184–91.

Baran J, Baj-Krzyworzeka M, Weglarczyk K, Szatanek R, Zembala M, Barbasz J, et al. Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother 2010; 59(6): 841–50.

Frank M, Manček-Keber M, Kržan M, Sodin-Šemrl S, Jerala R, Iglič A, et al. Prevention of microvesiculation by adhesion of buds to the mother cell membrane–A possible anticoagulant effect of healthy donor plasma. Autoimmun Rev 2008; 7(3): 240–5.

Šuštar V, Bedina-Zavec A, Štukelj R, Frank M, Ogorevc E, Janša R, et al. Post–prandial rise of microvesicles in peripheral blood of healthy human donors. Lipids Health Dis 2011; 10: 47.

Novak K, Štepec S, Hafner M, Ribnikar M, Markovič S. Characteristics of primary biliary cirrhosis in Slovenian patients. Analysis of 169 patients in the period from 1984 to 2010. Slov Med J 2012; 81(5): 372–82.

Ivanecz A, Jagrič T, Hazabent M, Horvat M, Potrč S. Characteristics and prognosis of young patients with gastric cancer in Slovenia. Slov Med J 2011; 80(1): 25–32.

Šuštar V, Janša R, Frank M, Hagerstrand H, Kržan M, Iglič A, et al. Suppression of membrane microvesiculation — A possible anticoagulant and anti-tumor progression effect of heparin. Blood Cells Mol Dis 2009; 42: 223–7.

Frank M, Sodin-Šemrl S, Rozman B, Potočnik M, Kralj-Iglič V. Effects of low-molecular-weight heparin on adhesion and vesiculation of phospholipid membranes–a possible mechanism for the treatment of hypercoagulability in antiphospholipid syndrome. Ann NY Acad Sci. Contemporary Chalanges in Autoimmunity 2009; 1173: 874–86.

Kralj-Iglič V, Šuštar V, Hagerstrand H, Frank M, Janša R. Suppression of membrane vesiculation: A possible anticoagulant, antimetastatic and anti-inflammatory effect of heparin. In: Piyathilake DE, Liang RH, eds. Heparin: Properties, Uses and Side Effects. Hauppauge, NY: Nova Science Publishers; 2011. p. 27–57.

Štukelj R, Šuštar V, Mrvar-Brečko A, Veranič P, Hägerstrand H, Kralj-Iglič V, et al. Suppression of membrane vesiculation as anticoagulant and anti-metastatic mechanism. Role of stability of narrow necks. Gen Physiol Biophys 2013; in press.

Urbanija J, Tomšič N, Lokar M, Ambrožič A, Čučnik S, Rozman B, et al. Coalescence of phospholipid membranes as a possible origin of anticoagulant effect of serum proteins. Chem Phys Lipids 2007; 150: 49–57.

How to Cite
1.
Ogorevc E, Bedina-Zavec A, Štukelj R, Šuštar V, Janša R. Increased vesiculability of platelets in 24 patients with gastrointestinal cancer. TEST ZdravVestn [Internet]. 1 [cited 15May2024];82(12). Available from: http://vestnik-dev.szd.si/index.php/ZdravVest/article/view/1030
Section
Original article