Table 1.

Summary of review articles addressing cancer cells exposed to microgravity conditions and 3D MCS formation.

Cell lineOriginMicrogravity
platform
TimelineFindingsRef.
Brain tumors
CS83iCTR-33n21Neural stem cellsISS39,6 dIncomplete cell division; impaired cytokinesis; multi-daughter cell division and alterations in the secretome32
Lung cancer
A549Lung carcinomaRWV/ hanging drop48, 72 dReverted epithelial-to-mesenchymal transition phenotype; impaired proliferation and cell morphological changes33
RPM24, 36, 48 hImpaired proliferation; presence of polynucleated cells; altered morphology of mitochondria and alterations in miRNAs involved in cell cycle regulation, apoptosis, and stress34
Calu-3Lung adenocarcinoma3 dIncreased estrogen sensitivity and altered spheroid stability12
NCI-H1703Lung squamosal carcinomaAltered spheroid stability
MCF-7Breast carcinoma72 hDisruption of actin and tubulin network in MCS; reductions in Vinculin; ERK inactivation and observed apoptosis35
Breast cancer
MDA-MB-231Breast carcinomaRPM72 hUpregulation of genes related to proliferation, cancer stemness and metastasis36
CRL2351Breast adenocarcinoma5 dGene analysis
Upregulation of genes related to proliferation, migration and cytoskeletal dynamics
Downregulation of genes involved in vesicle trafficking
Cytoskeletal rearrangement into a spherical shape
37
MDA-MB-231Breast carcinomaGravite system96 hUpregulation of Ras-like small GTPases; allterations in extracellular vesicles biogenesis and content38
MCF-7Breast carcinomaRPM
5, 10 dIncreased secretion of extracellular vesicles; increased exosome marker expression such as CD81, CD63, and CD939
MDA-MB-231Breast carcinoma14 dInvolvement of novel genes related to cellular signaling pathways (MAPK, PAM, and VEGF) in spheroids40
Thyroid cancer
FTC-133Follicular thyroid carcinomaISS12 dAltered exosome subpopulation42
5, 10 dChanges in gene expression of ECM components, cell adhesion factors, growth factors, cytokines and others such as RELA, ERK1, ERK255
RPM4 h, 3 dDexamethasone inhibits MCS formation; possible targets include ECM components, anti-adhesion molecules, cell junctions and phosphorylated glucocorticoid receptor14,57
1, 3 dMCS formation influenced by cell flask geometry, averaged gravity vector direction, angular velocity, fluid flow, and air bubbles13
Prostate cancer
PC-3Prostate adeno-carcinomaParabolic flight/Presence of F-actin stress fibers and pseudopodia; early differential expression of IL6 and CXCL8; alterations in regulatory lncRNAs and microRNAs61
RPM3, 5 dAlterations in VEGF signaling components, cytoskeleton components, ECM components, and the focal adhesion complex, suggest a more aggressive cancer phenotype under microgravity conditions62
0.5, 2, 4 and 24 hGene analysis
Upregulation of genes related to cytokine production such as IL6, CXCL8, and IL1A
Upregulation of genes related to cytoskeleton components and ECM components
Activated PAM signaling pathways in MCS
65
Gastrointestinal cancer
HGC-27Gastric carcinomaRCCS1,3 dInduced glycolytic pathways66
EPG85-257Gastric carcinoma24, 48, 72, 96 hAltered expression of multidrug resistance genes; cytoskeletal reorganization; changes in cell survival; increased cell susceptibility to chemotherapy67
PaCa-44Pancreatic adenocarcinomaRPM1, 7, 9 dPresence of an aggressive and metastatic stem cell-like phenotype; actin reorganization, enhanced epithelial-to-mesenchymal transition27
CFPAC-1Pancreatic adenocarcinoma
LS180Colorectal adenocarcinomaClinostat20 dVerified spheroids as a suitable model for pharmaceutical testing68
Skin cancer
HaCaTAneuploid immortal keratino-cyteClinostat2 hIncreased viability and mitochondrial activity; inhibited proliferation; altered cell morphology with a shrinked and rounded shape and lamellipodia but decreased filopodia and stress fibers; showed a disrupted actin network69
A375malignant melanoma
Cell lineOriginMicrogravity
platform
TimelineFindingsRef.
Brain tumors
CS83iCTR-33n21Neural stem cellsISS39,6 dIncomplete cell division; impaired cytokinesis; multi-daughter cell division and alterations in the secretome32
Lung cancer
A549Lung carcinomaRWV/ hanging drop48, 72 dReverted epithelial-to-mesenchymal transition phenotype; impaired proliferation and cell morphological changes33
RPM24, 36, 48 hImpaired proliferation; presence of polynucleated cells; altered morphology of mitochondria and alterations in miRNAs involved in cell cycle regulation, apoptosis, and stress34
Calu-3Lung adenocarcinoma3 dIncreased estrogen sensitivity and altered spheroid stability12
NCI-H1703Lung squamosal carcinomaAltered spheroid stability
MCF-7Breast carcinoma72 hDisruption of actin and tubulin network in MCS; reductions in Vinculin; ERK inactivation and observed apoptosis35
Breast cancer
MDA-MB-231Breast carcinomaRPM72 hUpregulation of genes related to proliferation, cancer stemness and metastasis36
CRL2351Breast adenocarcinoma5 dGene analysis
Upregulation of genes related to proliferation, migration and cytoskeletal dynamics
Downregulation of genes involved in vesicle trafficking
Cytoskeletal rearrangement into a spherical shape
37
MDA-MB-231Breast carcinomaGravite system96 hUpregulation of Ras-like small GTPases; allterations in extracellular vesicles biogenesis and content38
MCF-7Breast carcinomaRPM
5, 10 dIncreased secretion of extracellular vesicles; increased exosome marker expression such as CD81, CD63, and CD939
MDA-MB-231Breast carcinoma14 dInvolvement of novel genes related to cellular signaling pathways (MAPK, PAM, and VEGF) in spheroids40
Thyroid cancer
FTC-133Follicular thyroid carcinomaISS12 dAltered exosome subpopulation42
5, 10 dChanges in gene expression of ECM components, cell adhesion factors, growth factors, cytokines and others such as RELA, ERK1, ERK255
RPM4 h, 3 dDexamethasone inhibits MCS formation; possible targets include ECM components, anti-adhesion molecules, cell junctions and phosphorylated glucocorticoid receptor14,57
1, 3 dMCS formation influenced by cell flask geometry, averaged gravity vector direction, angular velocity, fluid flow, and air bubbles13
Prostate cancer
PC-3Prostate adeno-carcinomaParabolic flight/Presence of F-actin stress fibers and pseudopodia; early differential expression of IL6 and CXCL8; alterations in regulatory lncRNAs and microRNAs61
RPM3, 5 dAlterations in VEGF signaling components, cytoskeleton components, ECM components, and the focal adhesion complex, suggest a more aggressive cancer phenotype under microgravity conditions62
0.5, 2, 4 and 24 hGene analysis
Upregulation of genes related to cytokine production such as IL6, CXCL8, and IL1A
Upregulation of genes related to cytoskeleton components and ECM components
Activated PAM signaling pathways in MCS
65
Gastrointestinal cancer
HGC-27Gastric carcinomaRCCS1,3 dInduced glycolytic pathways66
EPG85-257Gastric carcinoma24, 48, 72, 96 hAltered expression of multidrug resistance genes; cytoskeletal reorganization; changes in cell survival; increased cell susceptibility to chemotherapy67
PaCa-44Pancreatic adenocarcinomaRPM1, 7, 9 dPresence of an aggressive and metastatic stem cell-like phenotype; actin reorganization, enhanced epithelial-to-mesenchymal transition27
CFPAC-1Pancreatic adenocarcinoma
LS180Colorectal adenocarcinomaClinostat20 dVerified spheroids as a suitable model for pharmaceutical testing68
Skin cancer
HaCaTAneuploid immortal keratino-cyteClinostat2 hIncreased viability and mitochondrial activity; inhibited proliferation; altered cell morphology with a shrinked and rounded shape and lamellipodia but decreased filopodia and stress fibers; showed a disrupted actin network69
A375malignant melanoma
Table 1.

Summary of review articles addressing cancer cells exposed to microgravity conditions and 3D MCS formation.

Cell lineOriginMicrogravity
platform
TimelineFindingsRef.
Brain tumors
CS83iCTR-33n21Neural stem cellsISS39,6 dIncomplete cell division; impaired cytokinesis; multi-daughter cell division and alterations in the secretome32
Lung cancer
A549Lung carcinomaRWV/ hanging drop48, 72 dReverted epithelial-to-mesenchymal transition phenotype; impaired proliferation and cell morphological changes33
RPM24, 36, 48 hImpaired proliferation; presence of polynucleated cells; altered morphology of mitochondria and alterations in miRNAs involved in cell cycle regulation, apoptosis, and stress34
Calu-3Lung adenocarcinoma3 dIncreased estrogen sensitivity and altered spheroid stability12
NCI-H1703Lung squamosal carcinomaAltered spheroid stability
MCF-7Breast carcinoma72 hDisruption of actin and tubulin network in MCS; reductions in Vinculin; ERK inactivation and observed apoptosis35
Breast cancer
MDA-MB-231Breast carcinomaRPM72 hUpregulation of genes related to proliferation, cancer stemness and metastasis36
CRL2351Breast adenocarcinoma5 dGene analysis
Upregulation of genes related to proliferation, migration and cytoskeletal dynamics
Downregulation of genes involved in vesicle trafficking
Cytoskeletal rearrangement into a spherical shape
37
MDA-MB-231Breast carcinomaGravite system96 hUpregulation of Ras-like small GTPases; allterations in extracellular vesicles biogenesis and content38
MCF-7Breast carcinomaRPM
5, 10 dIncreased secretion of extracellular vesicles; increased exosome marker expression such as CD81, CD63, and CD939
MDA-MB-231Breast carcinoma14 dInvolvement of novel genes related to cellular signaling pathways (MAPK, PAM, and VEGF) in spheroids40
Thyroid cancer
FTC-133Follicular thyroid carcinomaISS12 dAltered exosome subpopulation42
5, 10 dChanges in gene expression of ECM components, cell adhesion factors, growth factors, cytokines and others such as RELA, ERK1, ERK255
RPM4 h, 3 dDexamethasone inhibits MCS formation; possible targets include ECM components, anti-adhesion molecules, cell junctions and phosphorylated glucocorticoid receptor14,57
1, 3 dMCS formation influenced by cell flask geometry, averaged gravity vector direction, angular velocity, fluid flow, and air bubbles13
Prostate cancer
PC-3Prostate adeno-carcinomaParabolic flight/Presence of F-actin stress fibers and pseudopodia; early differential expression of IL6 and CXCL8; alterations in regulatory lncRNAs and microRNAs61
RPM3, 5 dAlterations in VEGF signaling components, cytoskeleton components, ECM components, and the focal adhesion complex, suggest a more aggressive cancer phenotype under microgravity conditions62
0.5, 2, 4 and 24 hGene analysis
Upregulation of genes related to cytokine production such as IL6, CXCL8, and IL1A
Upregulation of genes related to cytoskeleton components and ECM components
Activated PAM signaling pathways in MCS
65
Gastrointestinal cancer
HGC-27Gastric carcinomaRCCS1,3 dInduced glycolytic pathways66
EPG85-257Gastric carcinoma24, 48, 72, 96 hAltered expression of multidrug resistance genes; cytoskeletal reorganization; changes in cell survival; increased cell susceptibility to chemotherapy67
PaCa-44Pancreatic adenocarcinomaRPM1, 7, 9 dPresence of an aggressive and metastatic stem cell-like phenotype; actin reorganization, enhanced epithelial-to-mesenchymal transition27
CFPAC-1Pancreatic adenocarcinoma
LS180Colorectal adenocarcinomaClinostat20 dVerified spheroids as a suitable model for pharmaceutical testing68
Skin cancer
HaCaTAneuploid immortal keratino-cyteClinostat2 hIncreased viability and mitochondrial activity; inhibited proliferation; altered cell morphology with a shrinked and rounded shape and lamellipodia but decreased filopodia and stress fibers; showed a disrupted actin network69
A375malignant melanoma
Cell lineOriginMicrogravity
platform
TimelineFindingsRef.
Brain tumors
CS83iCTR-33n21Neural stem cellsISS39,6 dIncomplete cell division; impaired cytokinesis; multi-daughter cell division and alterations in the secretome32
Lung cancer
A549Lung carcinomaRWV/ hanging drop48, 72 dReverted epithelial-to-mesenchymal transition phenotype; impaired proliferation and cell morphological changes33
RPM24, 36, 48 hImpaired proliferation; presence of polynucleated cells; altered morphology of mitochondria and alterations in miRNAs involved in cell cycle regulation, apoptosis, and stress34
Calu-3Lung adenocarcinoma3 dIncreased estrogen sensitivity and altered spheroid stability12
NCI-H1703Lung squamosal carcinomaAltered spheroid stability
MCF-7Breast carcinoma72 hDisruption of actin and tubulin network in MCS; reductions in Vinculin; ERK inactivation and observed apoptosis35
Breast cancer
MDA-MB-231Breast carcinomaRPM72 hUpregulation of genes related to proliferation, cancer stemness and metastasis36
CRL2351Breast adenocarcinoma5 dGene analysis
Upregulation of genes related to proliferation, migration and cytoskeletal dynamics
Downregulation of genes involved in vesicle trafficking
Cytoskeletal rearrangement into a spherical shape
37
MDA-MB-231Breast carcinomaGravite system96 hUpregulation of Ras-like small GTPases; allterations in extracellular vesicles biogenesis and content38
MCF-7Breast carcinomaRPM
5, 10 dIncreased secretion of extracellular vesicles; increased exosome marker expression such as CD81, CD63, and CD939
MDA-MB-231Breast carcinoma14 dInvolvement of novel genes related to cellular signaling pathways (MAPK, PAM, and VEGF) in spheroids40
Thyroid cancer
FTC-133Follicular thyroid carcinomaISS12 dAltered exosome subpopulation42
5, 10 dChanges in gene expression of ECM components, cell adhesion factors, growth factors, cytokines and others such as RELA, ERK1, ERK255
RPM4 h, 3 dDexamethasone inhibits MCS formation; possible targets include ECM components, anti-adhesion molecules, cell junctions and phosphorylated glucocorticoid receptor14,57
1, 3 dMCS formation influenced by cell flask geometry, averaged gravity vector direction, angular velocity, fluid flow, and air bubbles13
Prostate cancer
PC-3Prostate adeno-carcinomaParabolic flight/Presence of F-actin stress fibers and pseudopodia; early differential expression of IL6 and CXCL8; alterations in regulatory lncRNAs and microRNAs61
RPM3, 5 dAlterations in VEGF signaling components, cytoskeleton components, ECM components, and the focal adhesion complex, suggest a more aggressive cancer phenotype under microgravity conditions62
0.5, 2, 4 and 24 hGene analysis
Upregulation of genes related to cytokine production such as IL6, CXCL8, and IL1A
Upregulation of genes related to cytoskeleton components and ECM components
Activated PAM signaling pathways in MCS
65
Gastrointestinal cancer
HGC-27Gastric carcinomaRCCS1,3 dInduced glycolytic pathways66
EPG85-257Gastric carcinoma24, 48, 72, 96 hAltered expression of multidrug resistance genes; cytoskeletal reorganization; changes in cell survival; increased cell susceptibility to chemotherapy67
PaCa-44Pancreatic adenocarcinomaRPM1, 7, 9 dPresence of an aggressive and metastatic stem cell-like phenotype; actin reorganization, enhanced epithelial-to-mesenchymal transition27
CFPAC-1Pancreatic adenocarcinoma
LS180Colorectal adenocarcinomaClinostat20 dVerified spheroids as a suitable model for pharmaceutical testing68
Skin cancer
HaCaTAneuploid immortal keratino-cyteClinostat2 hIncreased viability and mitochondrial activity; inhibited proliferation; altered cell morphology with a shrinked and rounded shape and lamellipodia but decreased filopodia and stress fibers; showed a disrupted actin network69
A375malignant melanoma
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