title: Malignancy of bladder cancer cells is enhanced by tumor-associated fibroblasts through a multifaceted cytokine-chemokine loop.
abstract: The microenvironment of tumor cells is critically involved in tumor development and progression. Tumor-associated fibroblasts (TAFs) represent a major constituent of the tumor stroma. Tumor cells are operative in the activation of TAFs, whereas TAFs in turn contribute to tumor cell malignancy. This report describes mechanisms of communication between fibroblasts and urinary bladder cancer (UBC) cells. Migration of bladder cancer cell lines RT112 and Cal-29, representing two different grades of dedifferentiation, was enhanced by cocultivation with TAFs. Conditioned medium from tumor cells induced the release of interleukin (IL)-8, hepatocyte growth factor (HGF), matrix metalloproteinase-2, granulocyte macrophage colony-stimulating factor, and monocyte chemotactic protein (MCP)-1 by TAFs. Tumor cell-derived IL-1α was identified as a major mediator of these stimulatory effects. Fibroblasts, on the other hand, exerted a migration and invasion stimulating influence on UBC cells. MCP-1 and HGF were shown to promote cell migration of both bladder cancer cell lines.
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Grimm
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Jennek
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Rajan
authors.initials: R
authors.lastname: Singh
authors.affiliation: Jena University Hospital, Department of Urology, Jena, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Enkelmann
authors.affiliation: Jena University Hospital, Department of Urology, Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Junker
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Rippaus
authors.affiliation: Jena University Hospital, Institute of Pathology, Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
authors.affiliation: Jena University Hospital, Institute of Biochemistry II, Jena, Germany. Electronic address: karlheinz.friedrich@med.uni-jena.de.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Friedrich
mesh_terms: D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005347:Fibroblasts / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017154:Stromal Cells / Q000473:pathology; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D017077:Culture Media, Conditioned; C066855:HGF protein, human; C508584:IL1A protein, human; D053582:Interleukin-1alpha; D016209:Interleukin-8; D017228:Hepatocyte Growth Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Interleukin-8; Matrix metalloproteinases; Microenvironment; Tumor stroma; Tumor-associated fibroblasts