Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Extrinsic Tme Stressors Promote Intra- and Intercellular Adaptations
1.2. Metabolic Reprogramming as a Priming Mechanism in Response to TME-Associated Stress
1.3. Chemorefractory HGSOC Highlights the Priming Capabilities of the TME
2. Differences in the Development of Chemorefractory and Chemoresistant HGSOC Populations
2.1. Hypoxia Confers Resistance in Refractory HGSOC
2.2. Hypoxia Alters HGSOC Secretome Profile
2.2.1. Cytokines
2.2.2. Growth Factors
2.2.3. EVs
2.3. Hypoxia Alters HGSOC Exosomes
2.4. Acquired Chemoresistance Is Achieved through Drug-Specific Adaptations and Induction of Therapy-Induced Senescence
2.5. Therapy-Induced Senescence and Escape as a Mechanism for Recurrent Disease
2.6. Therapy-Induced Chemoresistance Alters the HGSOC Secretome
2.6.1. Cytokines
2.6.2. Growth Factors
2.6.3. EVs
2.7. Role of Exosomes in Developing Chemoresistance
2.8. Changes in miRNAs
3. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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miRNAs | Function and Respective Targets |
---|---|
Hypoxia: miRNAs altered in hypoxia/hypoxic tissue and associated functional change | |
miRNA-181d-5p [189] | Increased expression in hypoxia-induced EVs; this enhanced M2 macrophage polarization and HGSOC cell migration and invasion |
miRNA-940 [192] | Increased expression in hypoxia, HGSOC patient ascites, and exosomes; HGSOC cell–macrophage exosome exchange enhanced M2 phenotype polarization |
miRNA-199a-3p [193] | Decreased expression reduced c-Met and AKT activity; this decreased proliferation, adhesion, and invasiveness |
miRNA-145 [194] | Suppressed HGSOC; downregulated HIF-1 and VEGF via p70S6K1 |
Therapy-induced: miRNAs altered in chemoresistant HGSOC cells or chemoresistance and associated functional change | |
miRNA-93 [195] | Increased expression in chemoresistant HGSOC cells; this altered cell survival mechanisms via PTEN |
miRNA-27a [196] | Increased expression in chemoresistant HGSOC cells; this increased MDR and PGP protein expression; inhibiting expression increased cell apoptosis via HIPK2 regulation |
miRNAs-130a/374 [197] | Increased expression reduced cisplatin sensitivity; miR-130a knockdown inhibited MDR1 expression and upregulated PTEN expression |
miRNA-142-5p [198] | Increased expression enhanced HGSOC cell platinum sensitivity via modulation of antiapoptotic proteins |
miRNA-1246 [199] | Increased expression in paclitaxel-resistant HGSOC cells and in patients with severe prognosis; this inhibited CAV-1 expression via the PDGFB receptor and altered cell proliferation |
miRNA-221/222 [200] | Increased expression conferred cisplatin resistance via the PTEN/PI3K/AKT signaling pathway |
miRNA-433 [201] | Increased expression induced paclitaxel resistance, HGSOC, and poor survival; this modulated HGSOC cell senescence and CDK6 activation |
miRNA-891-5p [202] | Increased expression in HGSOC patients and patients who exhibited carboplatin resistance; miRNA associated with DNA repair proteins and MYC regulator genes |
miRNAs-200a-c [190] | Increased expression in chemoresistant HGSOC patients; can serve as another diagnostic tool in addition to serum biomarker CA125 |
miRNA-106a/591 [203] | Increased miRNA-106a expression and decreased miRNA-591 expression in taxol-resistant cells; miRNA-106a targeted BCL-10 and caspase-7; miRNA-591 targeted ZEB1 |
miRNA-214 [204] | Decreased expression in chemoresistant HGSOC cells; played a crucial role in developing cisplatin resistance via PTEN |
miRNA-216b-5p [205] | Decreased expression in taxol-resistant HGSOC cells; overexpression of miRNA and knockdown of SNHG1 led to taxol sensitivity |
miRNA-34c [206] | Decreased expression in chemoresistant cells; directly targets SOX9, B-catenin, and c-MYC |
miRNA-383-5p [207] | Decreased expression reduced chemosensitivity via TRIM27; this modulated cell proliferation and HGSOC growth |
Let-7g [208] | Decreased expression in chemoresistant HGSOC patients; this induced EMT and resistance to platinum therapy |
Let-7i [51] | Decreased expression in cisplatin-resistant HGSOC; this activated BRCA1, RAD51, and DNA damage repair pathways |
miRNA-29 [209] | Decreased expression in cisplatin-resistant cells; this targeted ECM proteins, such as COL1A1, and modulated ERK1/2 and GSK3B |
miRNA-182-5p [210] | Decreased expression in cisplatin-resistant HGSOC cells; this miRNA targeted CDK6 |
miRNA-134 [211] | Decreased expression in taxol-resistant HGSOC cells; this targeted KAP2 and modulated cell survival and apoptosis |
miRNA-6126 [212] | Decreased expression correlated to poor prognosis; highly regulated in exosomes; overexpression reduced angiogenic phenotypes and migration; also acted as a tumor suppressor via integrin β1 |
miRNA-30a-5p [195] | Decreased expression in cisplatin-resistant HGSOC cells; this elevated apoptosis; exosome miRNA exchange altered chemosensitivity via SOX9 |
Overlapping miRNAs: miRNAs altered in both hypoxic and chemoresistant HGSOC cells | |
miRNA-21-3p [213] | Increased expression suppressed HGSOC cell apoptosis via APAF1 binding |
miRNA-223 [214] | Increased expression in hypoxia-induced exosomes; this promoted drug resistance in HGSOC cells via the PTEN–PI3K/AKT pathway |
miRNA-125b [189] | Increased expression in hypoxia-induced exosomes; this enhanced M2 macrophage polarization and increased HGSOC cell migration and invasion |
miRNA-210 [215] | Increased expression enhanced cancer cell viability and proliferation by targeting PTPN1 |
Refractory | Resistant | Both/Not Distinguished |
---|---|---|
Genomic | ||
CpG methylation [157,216] | BRCA1/2 mutation/amplification [59] | |
BRCA1 deletion [217,218] | ||
NF1 [218] | ||
RB1 [218] | ||
CDK12 [218] | ||
CSMD3 [218] | ||
FAT3 [218] | ||
GABRA6 [218] | ||
CCNE1 amplification [58,59,218] | ||
TP53 mutation [219] | ||
IGF2R deletion [220] | ||
MYC amplification [217,221] | ||
MDR1 [59] | ||
Rsf-1/HBXAP [222] | ||
NOTCH3 [223] | ||
Transcriptional | ||
JUN [56] | MDR1 [59] | FOXM1 [218] |
FOS [56] | ꞵ-tubulin III [140] | NOTCH [218] |
TNF [56] | p38a [182] | SNAIL [183] |
CXCR4 [56] | GSTpi [104] | SLUG [183] |
SNAI1 [56] | BCL-2 [172] | N-CAD [183] |
VIM [56] | Survivin [172] | p53 [67] |
GADD45B [56] | SMAD4 [183] | IL6 [56,216] |
MCL1 [56] | ||
HIFs [60] | ||
Tetraspanins [137] | ||
SNAREs [137] | ||
Rabs [137] | ||
Translational/post-translational | ||
AP-1 [120] | ꞵ-tubulin III [224] | STAT3 [90] |
NF-kB [120] | JNK [182] | Akt/mTOR [113] |
Cytokines | ||
IL-6 [110] | ||
IL-8 [110] | ||
IL-11 [110] | ||
IL-17 [110] | ||
IL-27 [110] | ||
IL-31 [110] | ||
Growth factors | ||
TGF-β [104,105,106] | ||
EGF [104,105,106] | ||
VEGF [104,105,106] | ||
TNF-α [118] |
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Lee, A.H.; Mejia Peña, C.; Dawson, M.R. Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations. Cancers 2022, 14, 1418. https://doi.org/10.3390/cancers14061418
Lee AH, Mejia Peña C, Dawson MR. Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations. Cancers. 2022; 14(6):1418. https://doi.org/10.3390/cancers14061418
Chicago/Turabian StyleLee, Amy H., Carolina Mejia Peña, and Michelle R. Dawson. 2022. "Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations" Cancers 14, no. 6: 1418. https://doi.org/10.3390/cancers14061418
APA StyleLee, A. H., Mejia Peña, C., & Dawson, M. R. (2022). Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations. Cancers, 14(6), 1418. https://doi.org/10.3390/cancers14061418