Survival Pathways Are Differently Affected by Microgravity in Normal and Cancerous Breast Cells

Abstract

Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be paradoxically protected from programmed cell death during weightlessness. These controversial results can be explained by considering the notion that the behavior of adherent cells dramatically diverges in respect to that of detached cells, organized into organoids-like, floating structures. We investigated both normal (MCF10A) and cancerous (MCF-7) breast cells and found that appreciable apoptosis occurs only after 72 h in MCF-7 cells growing in organoid-like structures, in which major modifications of cytoskeleton components were observed. Indeed, preserving cell attachment to the substrate allows cells to upregulate distinct Akt- and ERK-dependent pathways in MCF-7 and MCF-10A cells, respectively. These findings show that survival strategies may differ between cell types but cannot provide sufficient protection against weightlessness-induced apoptosis alone if adhesion to the substrate is perturbed.

The CellBox-2 Mission to the International Space Station: Thyroid Cancer Cells in Space

“…Furthermore, the gene expression of PXN was reduced in spaceflight samples. These results are in agreement with the data of a recent paper [35]. The cytoskeleton, integrins and focal adhesion factors are involved in anti-apoptotic strategies, depending on the cell type [35].…”

“…The downregulation of β 1 -integrin may inhibit cell adhesion to the ECM. In addition, MCF-7 breast cancer cells exposed to the rotating wall vessel (RWV) showed a decrease in β 1 -integrin protein [34], supporting the recent finding that focal adhesion is reduced in space and under s-µg conditions [35].…”

Alterations of Growth and Focal Adhesion Molecules in Human Breast Cancer Cells Exposed to the Random Positioning Machine

“…Integrin-β1, talin, vinculin, fibronectin, and laminin play key roles in focal adhesion processes and can give hint that focal adhesion is less in MCS. These findings are in agreement with the results of a recently published paper ( Monti et al, 2021 ). The adhesion process is very important for the survival strategy of cancer cells to antagonize cell death when the cells are exposed to the RPM.…”

“…The adhesion process is very important for the survival strategy of cancer cells to antagonize cell death when the cells are exposed to the RPM. The cytoskeleton, integrins and focal adhesion factors are involved in anti-apoptotic strategies, depending on the cell type ( Monti et al, 2021 ). No signs of apoptosis were found in MCF-7 cells after a 24-h RPM-exposure, which was paralleled by a reduction of vinculin and integrin-β1 in MCS ( Monti et al, 2021 ).…”

Simulated Microgravity Effects on Human Adenocarcinoma Alveolar Epithelial Cells: Characterization of Morphological, Functional, and Epigenetic Parameters

“…µG has been reported to interfere with mitochondrial activity, energetic metabolism, cell viability and proliferation, chemosensitivity, invasion and cell and organelle morphology in different biological systems (glioblastoma U87 cells [7]; malignant glioma [8]; normal and cancerous breast cells [9]; muscle cell [10]; lymphoblasts [11]. These studies evidence how cell types and lineages are differently affected by µG and several other factors not yet completely understood may concur to the final behavior.…”