title: CD248 facilitates tumor growth via its cytoplasmic domain.
abstract: BACKGROUND
  Stromal fibroblasts participate in the development of a permissive environment for tumor growth, yet molecular pathways to therapeutically target fibroblasts are poorly defined. CD248, also known as endosialin or tumor endothelial marker 1 (TEM1), is a transmembrane glycoprotein expressed on activated fibroblasts. We recently showed that the cytoplasmic domain of CD248 is important in facilitating an inflammatory response in a mouse model of arthritis. Others have reported that CD248 gene inactivation in mice results in dampened tumor growth. We hypothesized that the conserved cytoplasmic domain of CD248 is important in regulating tumor growth.
  
  
  METHODS
  Mice lacking the cytoplasmic domain of CD248 (CD248CyD/CyD) were generated and evaluated in tumor models, comparing the findings with wild-type mice (CD248WT/WT).
  
  
  RESULTS
  As compared to the response in CD248WT/WT mice, growth of T241 fibrosarcomas and Lewis lung carcinomas was significantly reduced in CD248CyD/CyD mice. Tumor size was similar to that seen with CD248-deficient mice. Conditioned media from CD248CyD/CyD fibroblasts were less effective at supporting T241 fibrosarcoma cell survival. In addition to our previous observation of reduced release of activated matrix metalloproteinase (MMP)-9, CD248CyD/CyD fibroblasts also had impaired PDGF-BB-induced migration and expressed higher transcripts of tumor suppressor factors, transgelin (SM22α), Hes and Hey1.
  
  
  CONCLUSIONS
  The multiple pathways regulated by the cytoplasmic domain of CD248 highlight its potential as a therapeutic target to treat cancer.
authors.affiliation: Vesalius Research Center, VIB, Herestraat 49, 9th floor, 3000 Belgium.
authors.forename: Margarida
authors.initials: M
authors.lastname: Maia
authors.forename: Astrid
authors.initials: A
authors.lastname: DeVriese
authors.forename: Tom
authors.initials: T
authors.lastname: Janssens
authors.forename: Michaël
authors.initials: M
authors.lastname: Moons
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Lories
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.forename: Edward M
authors.initials: EM
authors.lastname: Conway
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D043925:Angiogenesis Inducing Agents; D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D000077214:Becaplermin; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D012097:Repressor Proteins; C405694:Hairy, HRT1 protein; C499373:Notch3 protein, mouse; C051615:transgelin; C509258:tumor endothelial marker 1, mouse