Summary
Overcrowding and cell deformation lead to the shedding of apoptotic and live cells to maintain homeostasis in the epithelium. Recent studies have attempted to explain the effect of extrusion on epithelial homeostasis and tumor metastasis, but lack the requisite quantitative models for testing extrusion. Here, we designed a petri dish inversion model to detect the extrusion ability of both normal epithelial cells and epithelial cancer cells. Firstly, we found cell extrusion was observed in both normal epithelial cells (LO2 cells) and cancer cells; in confluent LO2 cell culture, certain cells were surrounded by their neighbors, suffered “collective attack”, and were then made round in shape. Green fluorescent protein (GFP)-labeled cancer cells were also found to be squeezed by normal LO2 cells. Using the petri dish inversion model, we quantified the number of extrusion cells, and demonstrated that the ability of cancer cell extrusion was related to the metastatic potential of cancer cell lines. Our findings provide a novel model to detect crowding-induced epithelial cell and cancer cell extrusion. This novel model provides a quantitative method for research into apoptotic and cancer cell extrusion, particularly in human hepatocellular carcinoma.
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References
Macara IG, Guyer R, Richardson G, et al. Epithelial homeostasis. Curr Biol, 2014,24(17):R815–825
Andrade D, Rosenblatt J. Apoptotic regulation of epithelial cellular extrusion. Apoptosis, 2011,16(5):491–501
Lubkov V, Bar-Sagi D. E-cadherin-mediated cell coupling is required for apoptotic cell extrusion. Curr Biol, 2014,24(8):868–874
Rosenblatt J, Raff MC, Cramer LP. An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr Biol, 2001,11(23):1847–1857
Gu Y, Rosenblatt J. New emerging roles for epithelial cell extrusion. Curr Opin Cell Biol, 2012,24(6):865–870
Katoh H, Fujita Y. Epithelial homeostasis: elimination by live cell extrusion. Curr Biol, 2012,22(11):R453-R455
Marinari E, Mehonic A, Curran S, et al. Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature, 2012,484(7395):542–545
Eisenhoffer GT, Loftus PD, Yoshigi M, et al. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature, 2012,484(7395):546–549
Porazinski S, de Navascues J, Yako Y, et al. EphA2 Drives the Segregation of Ras-Transformed Epithelial Cells from Normal Neighbors. Curr Biol, 2016,26(23):3220–3229
Slattum G, Gu Y, Sabbadini R, et al. Autophagy in oncogenic K-Ras promotes basal extrusion of epithelial cells by degrading S1P. Curr Biol, 2014,24(1):19–28
Marshall TW, Lloyd IE, Delalande JM, et al. The tumor suppressor adenomatous polyposis coli controls the direction in which a cell extrudes from an epithelium. Mol Biol Cell, 2011,22(21):3962–3970
Ohsawa S, Vaughen J, Igaki T. Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis. Dev Cell, 2018,44(3):284–296
Gu Y, Shea J, Slattum G, et al. Defective apical extrusion signaling contributes to aggressive tumor hallmarks. Elife, 2015,4:e04069
Slattum GM, Rosenblatt J. Tumour cell invasion: an emerging role for basal epithelial cell extrusion. Nat Rev Cancer, 2014,14(7):495–501
Han P, Fu Y, Liu J, et al. Netrin-1 promotes cell migration and invasion by down-regulation of BVES expression in human hepatocellular carcinoma. Am J Cancer Res, 2015,5(4):1396–1409
Slattum G, McGee KM, Rosenblatt J. P115 RhoGEF and microtubules decide the direction apoptotic cells extrude from an epithelium. J Cell Biol, 2009,186(5):693–702
Tanaka S, Shiraha H, Nakanishi Y, et al. Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma. Int J Cancer, 2012,131(11):2537–2546
Coloff JL, Brugge JS. Metabolic changes promote rejection of oncogenic cells. Nat Cell Biol, 2017,19(5):414–415
Vaughen J, Igaki T. Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia. Dev Cell, 2016,39(6):683–695
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This study was supported by the National Natural Science Foundation of China (No. 81472311, No. 81572419 and No. 81702396).
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Han, P., Li, Dx., Lei, Y. et al. A Potential Model for Detecting Crowding-induced Epithelial Cell and Cancer Cell Extrusion. CURR MED SCI 39, 391–395 (2019). https://doi.org/10.1007/s11596-019-2048-9
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DOI: https://doi.org/10.1007/s11596-019-2048-9