Tumor models in various Drosophila tissues

Abstract

The development of cancer is a complex multistage process. Over the past few decades, the model organism Drosophila melanogaster has been crucial in identifying cancer-related genes and pathways and elucidating mechanisms underlying growth regulation in development. Investigations using Drosophila has yielded new insights into the molecular mechanisms involved in tumor initiation and progression. In this review, we describe various tumor models that have been developed in recent years using different Drosophila tissues, such as the imaginal tissue, the neural tissue, the gut, the ovary, and hematopoietic cells. We discuss underlying genetic alterations, cancer-like characteristics, as well as similarities and key differences among these models. We also discuss how disruptions in stem cell division and differentiation result in tumor formation in diverse tissues, and highlight new concepts developed using the fly model to understand context-dependent tumorigenesis. We further discuss the progress made in Drosophila to explore tumor-host interactions that involve the innate immune response to tumor growth and the cachexia wasting phenotype. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Cancer > Stem Cells and Development Cancer > Molecular and Cellular Physiology.

Keywords: Drosophila; cachexia; cancer; stem cell; tumor.

FIGURE 1

Tumor models and related genes and pathways in different larval and adult tissues. (a) Larval tumor models in the brain, salivary gland imaginal ring, imaginal discs and hemocytes. (b) Adult tumor models in the gut, ovary, and testis

FIGURE 2

Tumor transplantation (xenograt) studies in Drosophila. First, primary tumors are induced in various tissues. They are then harvested and sectioned into small pieces. Next, the tumor pieces are injected into the abdomen of a host adult fly. The transplanted tumor can be harvested and replanted into new host flies for continued tumor growth

FIGURE 3

Metastasis in Drosophila tumor models. (a) The larval tumor cells metastasize to the gut, fat body, and trachea. (b) Tumor cells from the transplanted tumor metastasize to the gut, ovary, muscle, and brain. (c) The ISC tumor cells induced in the adult gut metastasize to the ovary and other tissues. (Arrows indicate metastasis directions)