title: A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer.
abstract: Small cell lung cancer (SCLC) is the lung neoplasia with the poorest prognosis, due to its high metastatic potential and chemoresistance upon relapse. Using the previously described mouse model for SCLC, we found that the tumors are often composed of phenotypically different cells with either a neuroendocrine or a mesenchymal marker profile. These cells had a common origin because they shared specific genomic aberrations. The transition from neuroendocrine to mesenchymal phenotype could be achieved by the ectopic expression of oncogenic Ras(V12). Crosstalk between mesenchymal and neuroendocrine cells strongly influenced their behavior. When engrafted as a mixed population, the mesenchymal cells endowed the neuroendocrine cells with metastatic capacity, illustrating the potential relevance of tumor cell heterogeneity in dictating tumor properties.
authors.affiliation: Division of Molecular Genetics and Center of Biomedical Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Calbo
authors.forename: Erwin
authors.initials: E
authors.lastname: van Montfort
authors.forename: Natalie
authors.initials: N
authors.lastname: Proost
authors.forename: Ellen
authors.initials: E
authors.lastname: van Drunen
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Ralph
authors.initials: R
authors.lastname: Meuwissen
authors.forename: Anton
authors.initials: A
authors.lastname: Berns
mesh_terms: D000818:Animals; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis