The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies

Abstract

The human prostate is a gland of the male reproductive tract, which together with the seminal vesicles, is responsible for most seminal fluid production. It is a common site of cancer, and unlike other glands, it typically enlarges in aging men. In flies, the male accessory glands make many major seminal fluid components. Like their human equivalents, they secrete proteins from several conserved families, including proteases, lectins, and cysteine-rich secretory proteins, some of which interact with sperm and affect fertility. A key protein, sex peptide, is not conserved in vertebrates but plays a central role in mediating long-term effects on females after mating. Although postmitotic, one epithelial cell type in the accessory glands, the secondary cell, continues to grow in adults. It secretes microvesicles called exosomes from the endosomal multivesicular body, which, after mating, fuse with sperm. They also appear to affect female postmating behavior. Remarkably, the human prostate epithelium also secretes exosomes, which fuse to sperm in vitro to modulate their activity. Exosomes from prostate and other cancer cells are increasingly proposed to play fundamental roles in modulating the tumor microenvironment and in metastasis. Here we review a diverse accessory gland literature, which highlights functional analogies between the male reproductive glands of flies and humans, and a critical role for extracellular vesicles in allowing seminal fluid to promote male interests within the female. We postulate that secondary cells and prostate epithelial cells use common mechanisms to control growth, secretion, and signaling, which are relevant to prostate and other cancers, and can be genetically dissected in the uniquely tractable fly model.

Control of Drosophila Growth and Survival by the Lipid Droplet-Associated Protein CG9186/Sturkopf

“…CG9186/sturkopf is expressed in the accessory gland of flies, and its expression is upregulated upon mating ( Figure 7D), which is often seen for accessory gland proteins. Only recently was the male accessory gland proposed to serve as a model to investigate certain aspects of mammalian prostate cancer (Ito et al, 2014;Wilson et al, 2017). Our study thus provides an entry point to investigate the intriguing possibility that a LD-associated protein is involved in the endocrine regulation of physiology.…”

Rab‐mediated trafficking in the secondary cells of Drosophila male accessory glands and its role in fecundity

“…This resource provides annotations based on a defined vocabulary for each Rab protein expressed in AGs and allows 3D localization tracking down to subcellular resolutions. Thus, our work maps out the maturation of the membrane/protein transport machinery in the AGs over time and adds valuable knowledge to the existing model describing the SC secretion system …”

DrosophilaSex Peptide Controls the Assembly of Lipid Microcarriers in Seminal Fluid

“…Seminal proteins are produced throughout adult life, but these proteins are only transferred to females sporadically. Some of these proteins are then rapidly activated via mechanisms that are thought to include proteolytic cleavage and pH changes in the female reproductive tract (discussed in (5)). Our data suggest that microcarriers could contribute to this activation process.…”

“…The paired Drosophila melanogaster male accessory glands (AGs) share functional similarities with both the prostate and seminal vesicles in humans (5). The monolayer epithelium of these glands is formed from two secretory cell types, about 1000 main cells and 40 secondary cells at the distal tip (6)(Fig.…”