Abstract
BackgroundLarvae of the tapeworm E. multilocularis cause alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. A population of stem cell-like cells, the germinative cells, is considered to drive the larval growth and development within the host. The molecular mechanisms controlling the behavior of germinative cells are largely unknown.Methodology/Principal findingsUsing in vitro cultivation systems we show here that the EGFR/ERK signaling in the parasite can promote germinative cell proliferation in response to addition of human EGF, resulting in stimulated growth and development of the metacestode larvae. Inhibition of the signaling by either the EGFR inhibitors CI-1033 and BIBW2992 or the MEK/ERK inhibitor U0126 impairs germinative cell proliferation and larval growth.Conclusions/SignificanceThese data demonstrate the contribution of EGF-mediated EGFR/ERK signaling to the regulation of germinative cells in E. multilocularis, and suggest the EGFR/ERK signaling as a potential therapeutic target for AE and perhaps other human cestodiasis.
Highlights
A population of pluripotent adult somatic stem cells, well known as “neoblasts”, has been extensively characterized and documented for free-living platyhelminthes [1,2,3,4,5]
To examine the impacts of epidermal growth factor (EGF) on the larval growth of E. multilocularis, metacestode vesicles were incubated in host cell-conditioned medium supplemented with recombinant human EGF
We found that 10 ng/mL or higher concentrations of EGF can greatly promote vesicle’s growth (S1 Fig)
Summary
A population of pluripotent adult somatic stem cells, well known as “neoblasts”, has been extensively characterized and documented for free-living platyhelminthes (flatworms) [1,2,3,4,5]. A population of undifferentiated cells, called “germinative cells”, is the only source for cell proliferation These germinative cells are totipotent and are thought to drive growth and development throughout the life cycle of cestodes [12, 15,16]. Protoscoleces can either mature into adult tapeworms if ingested by the definitive host (canids) or develop into metacestode vesicles when distributed in the intermediate host. This unique proliferation potential of E. multilocularis metacestode larvae is believed to be based upon the germinative cells, which are totipotent and have the ability for extensive self-renewal [15]. The molecular mechanisms controlling the behavior of germinative cells are largely unknown
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