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Transition from mesenchymal to bleb‐based motility is predominantly exhibited by CD133‐positive subpopulation of fibrosarcoma cells
Author(s) -
Chikina Aleksandra S.,
Rubtsova Svetla.,
Lomakina Maria E.,
Potashnikova Daria M.,
Vorobjev Ivan A.,
Alexandrova Antonina Y.
Publication year - 2019
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201800078
Subject(s) - biology , mesenchymal stem cell , lamellipodium , microbiology and biotechnology , pseudopodia , ht1080 , motility , cell migration , fibrosarcoma , cancer cell , sox2 , bleb (medicine) , homeobox protein nanog , actin , cancer research , cell , embryonic stem cell , induced pluripotent stem cell , cancer , biochemistry , genetics , trabeculectomy , neuroscience , glaucoma , gene
Background Information Metastatic disease is caused by the ability of cancer cells to reach distant organs and form secondary lesions at new locations. Dissemination of cancer cells depends on their migration plasticity – an ability to switch between motility modes driven by distinct molecular machineries. One of such switches is mesenchymal‐to‐amoeboid transition. Although mesenchymal migration of individual cells requires Arp2/3‐dependent actin polymerisation, amoeboid migration is characterised by a high level of actomyosin contractility and often involves the formation of membrane blebs. The acquisition of amoeboid motility by mesenchymal cells is often associated with enhanced metastasis. Results We studied the ability of mesenchymal HT1080 fibrosarcoma cells to switch to amoeboid motility. We induced the transition from lamellipodium‐rich to blebbing phenotype either by down‐regulating the Arp2/3 complex, pharmacologically or by RNAi, or by decreasing substrate adhesiveness. Each of these treatments induced blebbing in a subset of fibrosarcoma cells, but not in normal subcutaneous fibroblasts. A significant fraction of HT1080 cells that switched to blebbing behaviour exhibited stem cell‐like features, such as expression of the stem cell marker CD133, an increased efflux of Hoechst‐33342 and positive staining for Oct4, Sox2 and Nanog. Furthermore, the isolated CD133+ cells demonstrated an increased ability to switch to bleb‐rich amoeboid phenotype both under inhibitor's treatment and in 3D collagen gels. Conclusions Together, our data show a significant correlation between the increased ability of cells to switch between migration modes and their stem‐like features, suggesting that migration plasticity is an additional property of stem‐like population of fibrosarcoma cells. This combination of features could facilitate both dissemination of these cells to distant locations, and their establishment self‐renewal in a new microenvironment, as required for metastasis formation. Significance These data suggest that migration plasticity is a new feature of cancer stem‐like cells that can significantly facilitate their dissemination to a secondary location by allowing them to adapt quickly to challenging microenvironments. Moreover, it complements their resistance to apoptosis and self‐renewal potential, thus enabling them not only to disseminate efficiently, but also to survive and colonise new niches.