Table 3 Altered protein and gene expression in relation to spheroid formation in real and simulated microgravity
Tissue | Ref. | r-µG /s-µG (platform) | Cell type | Altered protein- or gene expression | Expression > = increase < = decrease | Described functions (protein-specific description available in Table S1) |
|---|---|---|---|---|---|---|
Thyroid | s-µG (RPM) | human follicular thyroid cancer cells | VEGFA, VEGFD, MSN, MMP3 | > | 3D growth promotion, angiogenesis and prevention of extracellular protein accumulation. | |
ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 | < | Genes coding for structural proteins that provide strength and rigidity to the cytoskeleton. | ||||
F-actin | Altered | |||||
s-µG (RPM) | Healthy thyroid cells | IL-8, OPN and IL-6. | Altered | |||
Thyroid tumor cells | NGAL | Altered | ||||
r-µG | Thyroid cancer cells | CAV1 interacts with tissue factor F3; together with TIMP1, A2M and APO-B | > | Inhibition of plasminogen activation so that plasmin is not accumulated, and spheroid formation is not triggered. Even when this process is supported by real microgravity. | ||
r-µG | Human follicular thyroid cancer cells | EGF | > | Mediates cellular proliferation, differentiation and survival. | ||
CTGF | < | Involved with proliferation, migration, angiogenesis and tumorigenesis. Overexpression promotes growth of thyroid cancer cells. | ||||
s-µG (RPM) | FTC-133 thyroid cancer cells | NF-kB p65 protein and apoptosis | > | |||
FTC-133 thyroid cancer cells (adherent) | IL-6, IL-8 and CD44 | > | ||||
ERK1/2, CAV2, TLN1 and CTGF | < | |||||
FTC-133 thyroid cancer cells (Spheroids) | ERK2, IL-6, CAV2, OPN, TLN1 and CTGF | > | ||||
s-µG (RPM) + s-µG (2D-Clinostat) | FTC-133 human thyroid cancer cells | CAV1, CTGF and eotaxin-1. | < | |||
s-µG (RPM) | VEGF | < | VEGF prevents apoptosis in thyroid carcinomas in an autocrine manner. The reduction could enhance apoptosis on RPM. | |||
Breast | s-µG (RPM) | MCF-7 Breast cancer cells (adherent) | IL8, VEGFA, and FLT1, ESR1, PGR1 | > | Genes and proteins involved in organization and regulation of the cell shape, angiogenesis, cell tip formation and membrane to membrane docking. | |
MCF-7 Breast cancer cells (multicellular spheroids) | PGR1 | > | ||||
ACTB, TUBB, EZR, RDX, FN1, VEGFA, FLK1 Casp9, Casp3, PRKCA mRNAs | < | |||||
s-µG (RPM) | Human breast cancer cells | e-cadherin | < | |||
e-cadherin auto-degradation proteins | > | Degradation of e-cadherin. | ||||
C-Src | > (>2x deviation) | |||||
s-µG (RPM) | MDA-MB-231 Breast cancer cells | ACTB, TUBB, FN1, FAK1, and PXN gene expression | Not altered | |||
MDA-MB-231 Breast cancer cells (adherent) | LAMA3, ITGB1 mRNAs | < | ||||
MDA-MB-231 Breast cancer cells (spheroids) | ITGB1, TLN1 and VCL mRNAs | < | ||||
MCF-7 breast cancer cells (Adherent) | FAK1, PXN, TLN1, VCL and CDH1 | < | ||||
MCF-7 breast cancer cells(Spheroids) | PXN, TLN and CDH1 | < | ||||
MCF-7 breast cancer cells | BCL9, MYC and JUN | Altered | Target genes of the Wnt/β-catenin signaling pathway | |||
Vasculature | s-µG (RPM) | Endothelial cells | Fibronectin and MCP-1 | > | ||
VEGF, IL-6, IL-8, MCP-1, ICAM-1, VCAM-1, NGAL and (RANTES) proteins | > | Genes and proteins involved in angiogenesis, tube formation, 3D growth, vascular and intercellular cell adhesion, inflammation. | ||||
r-µG (ISS) | Endothelial cells | Collagen and laminin | > | Extracellular matrix proteins. | ||
Growth factors, cytokines and ECM components | altered | |||||
s-µG (3D clinostat) | VEGF | > | ||||
r-µG + s-µG | IL-6 | > | ||||
Bone | s-µG (RPM) | Ewing’s Sarcoma cells (spheroids) | EWS/FLI1, CAV-1, CXR4 chemokine receptor and CD44 | > | ||
Ewing’s Sarcoma cells (adherent) | EWS/FLI1, CAV-1 | > | ||||
Ewing’s Sarcoma cells (both) | DKK2 and VEGFA | < | ||||
Tendon | s-µG (RPM) | Human tenocytes | COL1A1 (5,6 x increased), COL3A1, Tenascin C, Fibronectin (2,3x) and scleraxis (3,7x) | > | ||
Vimentin | Not altered |
