Helpful Bystanders

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Science  21 Nov 2008:
Vol. 322, Issue 5905, pp. 1165
DOI: 10.1126/science.322.5905.1165b

Although transformed cells can grow in artificial culture medium on plastic plates, in the body they thrive in very different surroundings. Individual cells are thought to become tumorigenic independently of their local environment, by acquiring genetic and epigenetic changes, although their neighbors may permit and possibly even nourish the growth of transformed cells. Indeed, tumorigenic cells have been shown to secrete signals that induce changes in the surrounding tissues.

Yang et al. show that in neurofibromatosis type 1 (NF1), a genetic disease that predisposes individuals to tumors such as neurofibromas, the premalignant cells and the cells that form the microenvironment cooperate to promote tumorigenesis. Neurofibromas form from malignant Schwann cells and are associated with peripheral nerves, which are infiltrated by inflammatory mast cells that are derived from the bone marrow. The disease is caused by germline mutations in the NF1 tumor suppressor gene; however, biallelic loss only in the Schwann cells is not sufficient for tumor progression. Instead, the authors find that a heterozygous Nf1 mutation in the nonmalignant infiltrating mast cells is necessary for neurofibroma formation. By blocking mast cell release from the bone marrow, they could delay disease progression. This work upgrades the role of the microenvironment from being permissive for tumorigenesis to being causative. Whether this phenomenon is limited to familial disorders or can also contribute to the development of sporadic tumors remains to be seen. — HP*

Cell 135, 437 (2008).

  • *Helen Pickersgill is a locum editor in Science's editorial department.

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