title: Enhanced eryptosis contributes to anemia in lung cancer patients.
abstract: OBJECTIVE
  Anemia is a common complication of malignancy, which could result from either compromised erythropoiesis or decreased lifespan of circulating erythrocytes. Premature suicidal erythrocyte death, characterized by cell shrinkage and phosphatidylserine (PS) externalization, decreases erythrocyte lifespan and could thus cause anemia. Here, we explored whether accelerated eryptosis participates in the pathophysiology of anemia associated with lung cancer (LC) and its treatment.
  
  
  METHODS
  Erythrocytes were drawn from healthy volunteers and LC patients with and without cytostatic treatment. PS exposure (annexin V-binding), cell volume (forward scatter), cytosolic Ca2+ (Fluo3 fluorescence), reactive oxygen species (ROS) production (DCFDA fluorescence) and ceramide formation (anti-ceramide antibody) were determined by flow cytometry.
  
  
  RESULTS
  Hemoglobin concentration and hematocrit were significantly lower in LC patients as compared to healthy controls, even though reticulocyte number was higher in LC (3.0±0.6%) than in controls (1.4±0.2%). The percentage of PS-exposing erythrocytes was significantly higher in LC patients with (1.4±0.1%) and without (1.2±0.3%) cytostatic treatment as compared to healthy controls (0.6±0.1%). Erythrocyte ROS production and ceramide abundance, but not Fluo3 fluorescence, were significantly higher in freshly drawn erythrocytes from LC patients than in freshly drawn erythrocytes from healthy controls. PS exposure of erythrocytes drawn from healthy volunteers was significantly more pronounced following incubation in plasma from LC patients than following incubation in plasma from healthy controls.
  
  
  CONCLUSIONS
  Anemia in LC patients with and without cytostatic treatment is paralleled by increased eryptosis, which is triggered, at least in part, by increased oxidative stress and ceramide formation.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Rosi
authors.initials: R
authors.lastname: Bissinger
authors.affiliation: Department of Internal Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Carla
authors.initials: C
authors.lastname: Schumacher
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Qadri
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Honisch
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Abaid
authors.initials: A
authors.lastname: Malik
authors.affiliation: Department of Microbial Genetics, University of Tübingen, Tübingen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.affiliation: Department of Internal Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kopp
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D016022:Case-Control Studies; D048429:Cell Size; D002518:Ceramides / Q000378:metabolism; D000072817:Eryptosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000378:metabolism; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000150:complications* / Q000188:drug therapy / Q000473:pathology
chemical_list: D002518:Ceramides; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; D002118:Calcium
keywords: anemia; carcinoma; cell shrinkage; ceramide; eryptosis