Distinct interactions between epithelial and mesenchymal cells control cell morphology and collective migration during sponge epithelial to mesenchymal transition

Abstract

Epithelial and mesenchymal cell types are basic for animal multicellularity and they have complementary functions coordinated by cellular interactions. Sponges are especially important model organisms to address the evolutionary basis of morphogenetic programs for epithelial and mesenchymal organization in animals. Evolutionary studies in sponges can contribute to the understanding of the mechanisms that control tissue maintenance and tumor progression in humans. In the present study, sponge mesenchymal and epithelial cells were isolated from the demosponge Hymeniacidon heliophila, and aggregate formation was observed by video microscopy. Epithelial‐mesenchymal interaction, epithelial transition, and cell migration led to sponge cell aggregation after drastic stress. Based on their different morphologies, adhesion specificities, and motilities, we suggest a role for different sponge cell types as well as complementary functions in cell aggregation. Micromanipulation under the microscope and cell tracking were also used to promote specific grafting‐host interaction, to further test the effects of cell type interaction. The loss of cell polarity and flattened shape during the epithelial to mesenchymal cell transition generated small immobile aggregates of round/amoeboid cells. The motility of these transited epithelial‐cell aggregates was observed by cell tracking using fluorescent dye, but only after interaction with streams of migratory mesenchymal cells. Cell motility occurred independently of morphological changes, indicating a progressive step in the transition toward a migratory mesenchymal state. Our data suggest a two‐step signaling process: (a) the lack of interaction between mesenchymal and epithelial cells triggers morphological changes; and (b) migratory mesenchymal cells instruct epithelial cells for directional cell motility. These results could have an impact on the understanding of evolutionary aspects of metastatic cancer cells.Highlights Morphogenetic movements observed in modern sponges could have a common evolutionary origin with collective cell migration of human metastatic cells. A sponge regenerative model was used here to characterize epithelial and mesenchymal cells, and for the promotion of grafting/host interactions with subsequent cell tracking. The transition from epithelial to mesenchymal cell type can be observed in sponges in two steps: (a) withdrawal of epithelial/mesenchymal cell interactions to trigger morphological changes; (b) migratory mesenchymal cells to induce epithelial cells to a collective migratory state.

RNAs in tumour‐derived extracellular vesicles and their significance in the tumour microenvironment

“…A process of cell morphology transformation from the epithelial into the mesenchymal state, known as EMT, can promote the spread of tumour cells via enhanced motility and invasive capabilities 152 . Multiple mechanisms are implicated in this process, especially cytoskeletal reorganization of the actin stress fibres, 153 changes in the expression of cell adhesion molecules (including E‐cadherin, N‐cadherin, vimentin, and fibronectin), 154 activation of MMP‐2 and MMP‐9 leading to degradation of the underlying basement membrane, 155,156 as well as the maintenance of autocrine growth factor signalling (namely TGF‐β, 157 Wnt, 158 Hedgehog, 159 and Hippo 160 ) to evade apoptosis and/or anoikis, a form of programmed cell death induced by detachment from the ECM 161,162 …”

Chemical factors induce aggregative multicellularity in a close unicellular relative of animals

“…1A) also exhibit cellular aggregation during fundamental processes to develop and maintain healthy multicellular tissues. From sponges and cnidarians to vertebrates, animal cells disaggregate and re-aggregate for spatial organization of tissues during the early stages of embryonic development (17)(18)(19), during inflammatory processes (20,21), and for tissue regeneration (22)(23)(24)(25)(26)(27)(28)(29). A few animal species have been conclusively demonstrated to use soluble chemical cues to regulate their aggregation phenotypes (6,23,30,31).…”