The effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7

Abstract

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. We hypothesized that the integration of environmental factors might induce specific cytoskeletal architecture patterns, characterized by quantitative image analysis. Human breast cancer cells MCF-7, flown in space in a photon capsule, were fixed after 1.5, 22, and 48 h in orbit. Cells subjected to weightlessness were compared with 1g in-flight and ground controls. Postflight, fluorescent labelings were performed to visualize cell proliferation (Ki-67), signal transduction (phosphotyrosine), three cytoskeleton components (microtubules, microfilaments, and intermediate filaments), and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network, and chromatin structure. In weightlessness, phosphotyrosine signal transduction was lower, more cells were cycling, and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade. Microtubules were altered in many cells. The perinuclear cytokeratin network was more loosely 'woven', and chromatin structure was modified. The prolongaion of mitosis can be explained by an alteration of microtubule self-organization in weightlessness, involving reaction-diffusion processes. The loosening of the perinuclear cytokeratin network and modification of chromatin distribution are in agreement with basic predictions of cellular tensegrity.

Gravitational Symmetry Breaking Leads to a Polar Liquid Crystal Phase of Microtubules In Vitro

“…Implications of the microgravity experiments and their explanation extend to cell behavior which was seen to be affected by microgravity in another space flight experiment [29]. As recently reported [30], in climbing plants competing for light energy, MTs create a twist obliquely oriented toward the cell's long axis in the root.…”

Proteomic Analysis of Mice Hippocampus in Simulated Microgravity Environment

“…The morphology of the microtubules in cardiac myocyte cytoskeleton and in MCF-7 cells became diffused under microgravity in space. 23,[35][36] In a microarray based study, it was reported that the expression of cytoskeletal molecules are disturbed, including putative mitochondria-anchoring proteins, A-kinase anchoring protein, and cytoplasmic dynein in space-flown rats. The loss of the cytoskeletal proteins resulted in dislocation of the mitochondria and a postulated leakage of reactive oxygen species from the mitochondria.…”

Exposure to modeled microgravity induces metabolic idleness in malignant human MCF‐7 and normal murine VSMC cells

“…This partial remodeling of the cell cycle was associated with reduced cell proliferation. Prolonged MCF-7 mitosis during MMG is not a new finding and has been attributed to weightlessness-induced alteration of microtubules [4]. Also Meyers et al [11] found that MMG alters proliferation rate, and reported that MMG, by decreasing integrin/MAPK signaling, contributes to reduced osteoblastogenesis during differentiation of human mesenchymal stem cells.…”

“…Microgravity induces adverse and metabolic effects in animals, humans and cellular systems [1][2][3][4]. We have evaluated the effects of microgravity on cell proliferation, glucose uptake, amino acid uptake and incorporation into proteins in neoplastic human breast cancer cells (MCF-7) and normal murine vascular smooth muscle cells (VSMC).…”