A Functional Role for Tumor Cell Heterogeneity in a Mouse Model of Small Cell Lung Cancer

J Calbo, E van Montfort, N Proost, E Drunen, Berna Beverloo, R Meuwissen, A Berns

Research output: Contribution to journalArticleAcademicpeer-review

283 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)244-256
Number of pages13
JournalCancer Cell
Volume19
Issue number2
DOIs
Publication statusPublished - 2011

Research programs

  • EMC MGC-02-96-01

Cite this