In Cancer Cell this week, researchers in France, Spain, and the Netherlands present a mouse model of small-cell lung cancer that they say shows a functional role for tumor cell heterogeneity. SCLC tumors are often composed of neuroendocrine and mesenchymal cells, and mesenchymal cells can endow neuroendocrine cells with metastatic capacity, the authors write. Oncoprotein RasV12 can make neuroendocrine cells transition to a mesenchymal phenotype, facilitating metastasis. "Crosstalk between mesenchymal and neuroendocrine cells strongly influenced their behavior," the authors write. "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."
Also in Cancer Cell this week, a team of researchers from across the US say they have evidence for a relationship between undifferentiated pleomorphic sarcoma and embryonal rhabdomyosarcoma. The precise cell of origin for embryonal rhabdomyosarcoma remains undefined, but by using Ptch1, p53, and Rb1 mouse models, the authors demonstrate that embryonal rhabdomyosarcoma and undifferentiated pleomorphic sarcoma "lie in a continuum, which satellite cells predisposed to giving rise to UPS." Therefore, the team adds, sarcoma phenotype is influenced by cell of origin and mutational profile.
And finally, researchers in Germany say that early relapse in acute lymphoblastic leukemia can be identified by time-to-leukemia in mice and is characterized by a gene signature in survival pathways. Short time-to-leukemia in the mice engrafted with ALL cells was strongly associated with high risk for early relapse, the authors write, "identifying an important prognostic factor." The high-risk phenotype was reflected by a gene signature which pointed to pathways like mTOR involved in cell growth and apoptosis. "The pathways identified can directly be targeted, thereby offering additional treatment approaches for these high-risk patients," the team adds.