Growth deregulation and interaction with host hemocytes contribute to tumor progression in a Drosophila brain tumor model

Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2221601120. doi: 10.1073/pnas.2221601120. Epub 2023 Aug 7.

Abstract

Tumors constantly interact with their microenvironment. Here, we present data on a Notch-induced neural stem cell (NSC) tumor in Drosophila, which can be immortalized by serial transplantation in adult hosts. This tumor arises in the larva by virtue of the ability of Notch to suppress early differentiation-promoting factors in NSC progeny. Guided by transcriptome data, we have addressed both tumor-intrinsic and microenvironment-specific factors and how they contribute to tumor growth and host demise. The growth promoting factors Myc, Imp, and Insulin receptor in the tumor cells are important for tumor expansion and killing of the host. From the host's side, hemocytes, professional phagocytic blood cells, are found associated with tumor cells. Phagocytic receptors, like NimC1, are needed in hemocytes to enable them to capture and engulf tumor cells, restricting their growth. In addition to their protective role, hemocytes may also increase the host's morbidity by their propensity to produce damaging extracellular reactive oxygen species.

Keywords: Drosophila allografts; Notch; brain tumor; macrophages; neural stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms* / genetics
  • Cell Differentiation
  • Drosophila
  • Drosophila Proteins* / genetics
  • Drosophila melanogaster / physiology
  • Hemocytes
  • Larva
  • Tumor Microenvironment

Substances

  • Drosophila Proteins