title: Tumor cells interact with red blood cells via galectin-4 - a short report.
abstract: BACKGROUND
  The ability of tumor cells to invade and metastasize is relevant to the process of cancer progression and, as such, it represents an obstacle to cancer cure. So far, limited information is available on interactions between circulating tumor cells and blood cells. It is well-documented that galectin-4 is upregulated in many types of tumor cells and is involved in metastasis. Here, we address the hypothesis that tumor cells may interact with red blood cells (RBCs) via galectin-4.
  
  
  METHODS
  High galectin-4 expressing colon, normal pancreatic and pancreatic cancer-derived cell lines (n = 5) were incubated with peripheral blood cells from different donors. Their interactions and associated proteins were examined by immunostaining and live cell imaging.
  
  
  RESULTS
  We found that (endogenous or exogenous) galectin-4 expressing tumor cells interact directly with RBCs. We also observed an accumulation of galectin-4 and human blood group antigens at the contact sites between these cells. By comparing the number of RBCs attaching to each tumor cell, we found that cells with high pre-incubation expression levels of galectin-4 attached significantly more RBCs than those with low expression levels (p < 1 × 10-7). Conversely, we found that RBC attachment induces galectin-4 expression in tumor cells.
  
  
  CONCLUSIONS
  From our data we conclude that tumor cells directly interact with red blood cells via galectin-4.
authors.affiliation: Molecular Cell Biology Lab, Zoology Department, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt. reham.helwa@sci.asu.edu.eg.|Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany. reham.helwa@sci.asu.edu.eg.|Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway. reham.helwa@sci.asu.edu.eg.
authors.forename: Reham
authors.identifier: http://orcid.org/0000-0003-1009-0786
authors.initials: R
authors.lastname: Helwa
authors.affiliation: Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Anette
authors.initials: A
authors.lastname: Heller
authors.affiliation: Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Oncology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.affiliation: Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Bauer
mesh_terms: D002449:Cell Aggregation / Q000235:genetics; D002450:Cell Communication / Q000235:genetics*; D045744:Cell Line, Tumor; D004912:Erythrocytes / Q000166:cytology*; D037541:Galectin 4 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D037541:Galectin 4
keywords: Blood; Cancer cells; Erythrocytes; Galectin-4; Interactions