title: Cooperate concept of metastasis: site-specific requirement of activated differentiation and dynamic deterioration.
abstract: Cancer metastasis results from positive and negative cellular events such as constitutive activation of oncogenes (cOA) or genetic losses (GL) being modulated by downstream signals of epithelial-mesenchymal or mesenchymal-epithelial transition, thus constituting master programs of metastatic phenotype and site specificity. To address the complex nature of these programs, we introduced clinical and phenotypic markers like tumor size, grade, cellular shape, or expression of E-cadherin in 27 colon cancer (CC) patients (cOA and GL), and 41 patients with gastrointestinal stromal tumors (GIST, cOA) to produce scores of cOA and GL. Scores of cOA were highest in case of hepatic and lower in case of an isolated peritoneal spread (GIST), or (CC) of both, cOA and GL, highest in case of a combined hepatic and peritoneal spread and lower in case of an isolated peritoneal spread; but in case of an isolated hepatic spread, scores of cOA were high and low of GL. This indicates a differential contribution of cellular dissociation and recognition in site-specific metastasis, of cOA predominantly in production of hepatic and in the case of GL of serosal spread.
authors.affiliation: Department of Surgery, University Hospital of Freiburg, Freiburg, Germany. c.wilmanns@johanniter-rheinhausen.de
authors.forename: C
authors.initials: C
authors.lastname: Wilmanns
authors.forename: S
authors.initials: S
authors.lastname: Steinhauer
authors.forename: J
authors.initials: J
authors.lastname: Großmann
authors.forename: A
authors.initials: A
authors.lastname: Schmitt-Gräff
authors.forename: G
authors.initials: G
authors.lastname: Ruf
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009857:Oncogenes; D010641:Phenotype; D015398:Signal Transduction
chemical_list: D015820:Cadherins