The Kinase MIRK/DYRK1B Mediates a Reversible Quiescent State in a Subset of Ovarian, Pancreatic and Colon Cancers

In orthodox seeds the cell division within the embryo meristems arrests during maturation at embryo moisture content (MC) 65% to 47%, and the maturation completion and transition of seeds to quiescent state occurs at MC about 10%. The arrest of cycling happens asynchronously in different meristematic tissues during desiccation: first in shoot and then in root. The aim of this work was to define a mitotic activity dynamics in recalcitrant seeds with the high MC at maturation end and the absence of quiescent state characteristic of it. The object was seeds of Acer saccharinum, using widely for planting of greenery in Kiev city. The mitotic activity was determined in 0.5 mm of the embryo root pole (RP) and 0.5 mm of the shoot pole with embryo leaves (SP). The A. sachharinum seeds completed them maturation at MC 53% (FW basis). During maturation the mitotic index (MI) in RP decreased from 3.2% in immature seeds (at embryos MC 80%) to 0 in mature seeds and in SP–from 5.4% to 3.3%, respectively. Cell division in SP arrested by dehydration of mature embryos to MC 46% by PEG 6000 (30%). The seeds lost viability by desiccation to MC 34%. The mature seeds were able to germinate immediately after abscission. During seed germination the cell division reactived in RP and increased in SP already before root protrusion. In plantlets 10–15 mm long the MI increased to 8% in RP and 12% in SP. Thus, the strategy of immediate germination of recalcitrant A. sachharinum seeds includes a preservation of cell division in SP of mature embryos, in contrast with orthodox seeds, and high mitotic activity levels in meristems of germinating embryos before and after root protrusion.

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Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽

10.1136/gutjnl-2020-323363 ◽

2021 ◽

pp. gutjnl-2020-323363

Author(s):

Ester Pagano ◽

Joshua E Elias ◽

Georg Schneditz ◽

Svetlana Saveljeva ◽

Lorraine M Holland ◽

...

Keyword(s):

Colon Cancer ◽

Tumour Growth ◽

Tumour Microenvironment ◽

Tube Formation ◽

Tissue Remodelling ◽

Colon Cancers ◽

Inflammatory Bowel ◽

Ion Pumping ◽

G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

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Treating colon cancers with a non-conventional yet strategic approach: An overview of various nanoparticulate systems

Journal of Controlled Release ◽

10.1016/j.jconrel.2021.06.008 ◽

2021 ◽

Author(s):

B. Navya Ajitkumar ◽

Lalit Kumar

Keyword(s):

Colon Cancers ◽

Strategic Approach ◽

Nanoparticulate Systems

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Dynamic changes of podocytes caused by fibroblast growth factor 2 in culture

Cell and Tissue Research ◽

10.1007/s00441-021-03511-x ◽

2021 ◽

Author(s):

Eishin Yaoita ◽

Masaaki Nameta ◽

Yutaka Yoshida ◽

Hidehiko Fujinaka

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 2 ◽

Quiescent State ◽

Fibroblast Growth ◽

Gene Expressions ◽

Dynamic Changes ◽

Ki 67

AbstractFibroblast growth factor 2 (FGF2) augments podocyte injury, which induces glomerulosclerosis, although the mechanisms remain obscure. In this study, we investigated the effects of FGF2 on cultured podocytes with interdigitating cell processes in rats. After 48 h incubation with FGF2 dynamic changes in the shape of primary processes and cell bodies of podocytes resulted in the loss of interdigitation, which was clearly shown by time-lapse photography. FGF2 reduced the gene expressions of constituents of the slit diaphragm, inflections of intercellular junctions positive for nephrin, and the width of the intercellular space. Immunostaining for the proliferation marker Ki-67 was rarely seen and weakly stained in the control without FGF2, whereas intensely stained cells were frequently found in the presence of FGF2. Binucleation and cell division were also observed, although no significant increase in cell number was shown. An in vitro scratch assay revealed that FGF2 enhanced migration of podocytes. These findings show that FGF2 makes podocytes to transition from the quiescent state into the cell cycle and change their morphology due to enhanced motility, and that the culture system in this study is useful for analyzing the pathological changes of podocytes in vivo.

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