Lung Cancer Stem Cell Lose Their Stemness Default State after Exposure to Microgravity

Pisanu, Maria Elena; Noto, Alessia; Vitis, Claudia De; Masiello, Maria Grazia; Coluccia, Pierpaolo; Proietti, Sara; Giovagnoli, Maria Rosaria; Rícci, Alberto; Giarnieri, Enrico; Cucina, Alessandra; Ciliberto, Gennaro; Bizzarri, Mariano; Mancini, Rita

doi:10.1155/2014/470253

Cited by 54 publications

(44 citation statements)

References 34 publications

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“…The ultimate evidence that cancer cells lose their malignancy under microgravity is still missing, but there are some clues in this direction. Lung cancer stem cells have been observed to lose their stemness under microgravity, downregulating Oct-4 and Nanog expression 29 . Thyroid cancer cells have shown higher production of antiproliferative and antimetastatic factors 30 .…”

Section: Discussionmentioning

confidence: 99%

Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity

Kraus

Luetzenberg

Abuagela

et al. 2017

MLTJ

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SummaryBackground: For tendon tissue engineering, tenocyte-seeded scaffolds are a promising approach. Under conventional 2D culture however, tenocytes show rapid senescene and phenotype loss. We hypothesized that phenotype loss could be counteracted by simulated microgravity conditions. Methods: Human tenocytes were exposed to microgravity for 9 days on a Random Positioning Machine (RPM). Formation of 3D-structures (spheroids) was observed under light microscopy, gene expression was measured by realtime PCR. Cells under conventional 2D-culture served as control group. Results: Simulated microgravity reached a value of as low as 0.003g. Spheroid formation was observed after 4 days, and spheroids showed stable existance to the end of the observation period. After 9 days, spheroids showed a significantly higher gene expression of collagen 1 (Col1A1) compared to adherent cells under microgravity (4.4x, p=0.04) and compared to the control group (5.6x, p=0.02). Gene expression of collagen 3 (COL3A1) was significantly increased in spheroids compared to the control group (2.3x, p=0.03). Gene expressions of the extracellular matrix genes Tenascin C und Fibronectin (TNC and FN) were increased in adherent cells under microgravity compared to the 1g-control group, not reaching statistical significance (p=0.1 and p=0.3). For the gene expression of vimentin, no significant alteration was observed both in the adherent cells and in the spheroids compared to the 1g control group. Gene expression of the tenocyte-specific transcription factor scleraxis (SCX) was significantly increased in spheroids compared to the control group (3.7x, p=0.03). Conclusion: Simulated microgravity could counteract tenocyte senescence in vitro and serve as a promising model for scaffold-free 3D cell culturing and tissue engineering. Level of evidence: V (laboratory study).

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Section: Discussionmentioning

confidence: 99%

Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity

Kraus

Luetzenberg

Abuagela

et al. 2017

MLTJ

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“…It has since become clear that system level changes occur in microgravity fields (Crawford‐Young, ). More specifically, microgravity has been shown to affect cell morphology (Crawford‐Young, ; Testa et al., ), cytoskeletal organization (Masiello et al., ), early development (reviewed by Ogneva, ; see also Dournon, ), the likelihood of the open state of ion channels (Goldermann & Hanke, ), gene expression profiles (Pardo et al., ), differentiation (Pisanu et al., ), and apoptosis (Monici et al., ). Microgravity, in most cases so far, has been shown to be an inhibitor of tissue growth and regeneration in mammalian tissues (Blaber et al., ).…”

Section: Introductionmentioning

confidence: 99%

Planarian regeneration in space: Persistent anatomical, behavioral, and bacteriological changes induced by space travel

et al. 2017

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Regeneration is regulated not only by chemical signals but also by physical processes, such as bioelectric gradients. How these may change in the absence of the normal gravitational and geomagnetic fields is largely unknown. Planarian flatworms were moved to the International Space Station for 5 weeks, immediately after removing their heads and tails. A control group in spring water remained on Earth. No manipulation of the planaria occurred while they were in orbit, and space‐exposed worms were returned to our laboratory for analysis. One animal out of 15 regenerated into a double‐headed phenotype—normally an extremely rare event. Remarkably, amputating this double‐headed worm again, in plain water, resulted again in the double‐headed phenotype. Moreover, even when tested 20 months after return to Earth, the space‐exposed worms displayed significant quantitative differences in behavior and microbiome composition. These observations may have implications for human and animal space travelers, but could also elucidate how microgravity and hypomagnetic environments could be used to trigger desired morphological, neurological, physiological, and bacteriomic changes for various regenerative and bioengineering applications.

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“…In cervical cancer, ALDH1-positive cells, like other solid tumors, are known to be more tumorigenic than negative ones, and we used ALDH1 as a marker of cervical CSCs (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). First, using the cervical cancer cell line CaSki we confirmed that the expression of PAI-1 was significantly increased by changing coatings of culture plates as described (35), especially collagen IV-coating, confirmed by enzyme-linked immunosorbent assay (ELISA).…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells

Sato

Kawana

Adachi

et al. 2015

International Journal of Oncology

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Abstract. The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

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Lung Cancer Stem Cell Lose Their Stemness Default State after Exposure to Microgravity

Cited by 54 publications

References 34 publications

Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity

Spheroid formation and modulation of tenocyte-specific gene expression under simulated microgravity

Planarian regeneration in space: Persistent anatomical, behavioral, and bacteriological changes induced by space travel

Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells

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