This vignette from the R package JMDplots version 1.2.19-9 shows chemical metrics for secreted proteins that are differentially expressed in hypoxia compared to control conditions. The analysis is described in more detail in a paper (Dick, 2021). Abbreviations:
Differences are calculated as (median value for up-regulated proteins) - (median value for down-regulated proteins). Dashed lines enclose the 50% confidence region for highest probability density.
In the table, values of ΔZC and ΔnH2O are multiplied by 1000, values of ΔMW are multiplied by 100, and negative values are shown in bold. Abbreviations:
| set | reference (description) | ndown | nup | ΔZC | ΔnH2O | ΔnAA | ΔMW |
|---|---|---|---|---|---|---|---|
| a |
BRA+10 (placental secretome)
|
41 | 22 | -26 | -5 | -10 | 108 |
| b |
PTD+10 (A431 squamous carcinoma cells Hx48)
|
38 | 78 | -27 | 68 | -174 | -10 |
| c |
PTD+10 (A431 squamous carcinoma cells Hx72)
|
43 | 66 | -1 | 65 | -296 | 44 |
| d |
JVC+12 (endothelial cell-derived exosomes)
|
64 | 45 | 0 | 84 | -229 | -45 |
| e |
SKA+13 (cytotrophoblast-derived exosomes)
|
38 | 25 | 46 | 38 | 72 | -121 |
| f |
SRS+13a (pMSC 3 / 1 % O2)
|
193 | 72 | 14 | -6 | 84 | 62 |
| g |
SRS+13a (pMSC 8 / 1 % O2)
|
193 | 75 | 6 | -19 | 167 | 111 |
| h |
LRS+14 (myoblast secretome)
|
52 | 29 | 40 | -46 | 276 | -140 |
| i |
YKK+14 (U373MG glioma cells soluble)
|
45 | 22 | 66 | -27 | -54 | 49 |
| j |
YKK+14 (U373MG glioma cells exosome)
|
56 | 40 | 52 | -38 | -100 | 105 |
| k |
CRS+15 (MDA-MB-231 breast cancer parental cells)
|
28 | 25 | 2 | -53 | 32 | -142 |
| l |
CRS+15 (MDA-BT breast cancer bone tropic cells)
|
20 | 79 | 36 | -84 | 185 | -122 |
| m |
RTA+15 (LNCaP and PC3 prostate cancer cell exosomes)
|
16 | 111 | -13 | 35 | -170 | 86 |
| n |
RSE+16 (adipose-derived stem cells)
|
66 | 50 | 27 | -13 | 58 | 50 |
| o |
CGH+17 (mouse cardiac fibroblasts exosomes)
|
73 | 71 | 40 | -68 | 110 | -112 |
| p |
CGH+17 (mouse cardiac fibroblasts secretome)
|
47 | 75 | 5 | -54 | -31 | -123 |
| q |
CLY+18 (HCT116 colon cancer cells secretome)
|
104 | 88 | 29 | -29 | -146 | -113 |
| r |
DWW+18 (ovarian cancer cell exosomes)
|
22 | 102 | 7 | -1 | 4 | 194 |
| s |
FPR+18 (endothelial progenitor cells)
|
41 | 42 | -1 | 20 | 167 | -8 |
| t |
ODS+18 (AC10 ventricular cardiomyocyte extracellular vesicles)
|
14 | 60 | -5 | 20 | -110 | -286 |
| u |
CWG+19 (U87-MG glioma cell extracellular vesicles)
|
980 | 1034 | 1 | 2 | 44 | -22 |
| v |
KAN+19 (cancer-associated fibroblasts secretome)
|
33 | 26 | -20 | -5 | -293 | 242 |
| w |
NJVS19 (cancer-associated myofibroblasts)
|
96 | 54 | 29 | -23 | 63 | -105 |
| x |
NJVS19 (normal tissue myofibroblasts)
|
143 | 233 | -29 | 57 | -188 | 97 |
| y |
PDT+19 (mouse melanoma B16-F0 exosomes)
|
219 | 988 | 2 | 14 | 46 | 30 |
Gene names or other identifiers were converted to UniProt accession numbers using the UniProt mapping tool.
a. Tables 2 and 3 of Blankley et al. (2010). b. c. Gene names from Supplementary Table S1 of Park et al. (2010), filtered with p-value < 0.05, expression ratio > 1.3 or < 1/1.3 and EF < 2. d. Extracted from Supplementary Table SIII of de Jong et al. (2012): median values of peptide quantification (omitting proteins identified with less than 5 peptides that have different signs of log2 values); differentially expressed proteins identifed using a log2 cutoff of 0.2. e. Extracted from Table 1 of Salomon et al. (2013a), to include proteins exclusively identified in 1% or 8% O2. f. g. Extracted from Table 1 of Salomon et al. (2013b), including unique proteins for 1%, 3%, and 8% O2. h. GI numbers from Supplementary Data 6 of Li et al. (2014). i. j. Extracted from Table S1 of Yoon et al. (2014), to include proteins identified by at least 2 unique peptides and surpassing a log2 cutoff of 0.5 in soluble or exosome fractions. k. l. Gene names from Supplementary Information Table 1 of Cox et al. (2015), filtered to include proteins with log2 fold change between air and hypoxia > 0.2 or < -0.2. m. Gene names from Supporting Information Tables S1 (normoxic) and S2 (hypoxic) of Ramteke et al. (2015), filtered to include proteins that were exclusively identified in either condition. n. Gene names from Tables 1 and 2 of Riis et al. (2016). o. p. Extracted from Tables S2A (exosomes) and S2B (secretome) of Cosme et al. (2017), keeping proteins with FDR < 0.05. q. Supplementary Tables S8-S9 (secretome) of Chen et al. (2018). r. Supplementary Table 1 of Dorayappan et al. (2018). s. Table S2 of Felice et al. (2018). t. Supplementary Material Tables S1 and S2 of Ontoria-Oviedo et al. (2018), filtered to include proteins exclusively identified in hypoxia or normoxia. u. Supplementary Tables 1 and 2 of Chandran et al. (2019), filtered to include proteins uniquely identified in either hypoxia or normoxia. v. Proteins identified as up- or down-regulated > 1 SD in Data File S1 of Kugeratski et al. (2019) (pooled data from sheets “Soluble Secretome” and “EVs”). w. x. Extracted from proteinGroups.txt in ProteomeXchange Dataset PXD008104 (Najgebauer et al., 2019). Expression ratios between hypoxia and normoxia were calculated from LFQ intensity values, and proteins were classified as up- or down-regulated if they had expression ratios > 1.2 or < 1/1.2 in all three experiments for one cell type (CAM or NTM). The Majority protein IDs and mean values of the expression ratios were saved in the data file. y. Supplementary Table 2 of Park et al. (2019), filtered with log2 fold-change cutoff of 1.
Blankley RT, Robinson NJ, Aplin JD, Crocker IP, Gaskell SJ, Whetton AD, Baker PN, Myers JE. 2010. A gel-free quantitative proteomics analysis of factors released from hypoxic-conditioned placentae. Reproductive Sciences 17:247–257. DOI: 10.1177/1933719109351320.
Chandran VI, Welinder C, Gonçalves de Oliveira K, Cerezo-Magaña M, Månsson A-S, Johansson MC, Marko-Varga G, Belting M. 2019. Global extracellular vesicle proteomic signature defines U87-MG glioma cell hypoxic status with potential implications for non-invasive diagnostics. Journal of Neuro-Oncology 144:477–488. DOI: 10.1007/s11060-019-03262-4.
Chen J-T, Liu C-C, Yu J-S, Li H-H, Lai M-C. 2018. Integrated omics profiling identifies hypoxia-regulated genes in HCT116 colon cancer cells. Journal of Proteomics 188:139–151. DOI: 10.1016/j.jprot.2018.02.031.
Cosme J, Guo H, Hadipour-Lakmehsari S, Emili A, Gramolini AO. 2017. Hypoxia-induced changes in the fibroblast secretome, exosome, and whole-cell proteome using cultured, cardiac-derived cells isolated from neonatal mice. Journal of Proteome Research 16:2836–2847. DOI: 10.1021/acs.jproteome.7b00144.
Cox TR, Rumney RMH, Schoof EM, Perryman L, Høye AM, Agrawal A, Bird D, Latif NA, Forrest H, Evans HR, Huggins ID, Lang G, Linding R, Gartland A, Erler JT. 2015. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature 522:106–110. DOI: 10.1038/nature14492.
de Jong OG, Verhaar MC, Chen Y, Vader P, Gremmels H, Posthuma G, Schiffelers RM, Gucek M, Balkom BWM van. 2012. Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. Journal of Extracellular Vesicles 1:18396. DOI: 10.3402/jev.v1i0.18396.
Dorayappan KDP, Wanner R, Wallbillich JJ, Saini U, Zingarelli R, Suarez AA, Cohn DE, Selvendiran K. 2018. Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: A novel mechanism linking STAT3/Rab proteins. Oncogene 37:3806–3821. DOI: 10.1038/s41388-018-0189-0.
Felice F, Piras AM, Rocchiccioli S, Barsotti MC, Santoni T, Pucci A, Burchielli S, Chiellini F, Ucciferri N, Solaro R, Altomare A, Cecchettini A, Stefano RD. 2018. Endothelial progenitor cell secretome delivered by novel polymeric nanoparticles in ischemic hindlimb. International Journal of Pharmaceutics 542:82–89. DOI: 10.1016/j.ijpharm.2018.03.015.
Kugeratski FG, Atkinson SJ, Neilson LJ, Lilla S, Knight JRP, Serneels J, Juin A, Ismail S, Bryant DM, Markert EK, Machesky LM, Mazzone M, Sansom OJ, Zanivan S. 2019. Hypoxic cancer-associated fibroblasts increase NCBP2-AS2/HIAR to promote endothelial sprouting through enhanced VEGF signaling. Science Signaling 12:eaan8247. DOI: 10.1126/scisignal.aan8247.
Li X, Ren Y, Sorokin V, Poh KK, Ho HH, Lee CN, Kleijn D de, Lim SK, Tam JP, Sze SK. 2014. Quantitative profiling of the rat heart myoblast secretome reveals differential responses to hypoxia and re-oxygenation stress. Journal of Proteomics 98:138–149. DOI: 10.1016/j.jprot.2013.12.025.
Najgebauer H, Jarnuczak AF, Varro A, Sanderson CM. 2019. Integrative omic profiling reveals unique hypoxia induced signatures in gastric cancer associated myofibroblasts. Cancers 11:263. DOI: 10.3390/cancers11020263.
Ontoria-Oviedo I, Dorronsoro A, Sánchez R, Ciria M, Gómez-Ferrer M, Buigues M, Grueso E, Tejedor S, García-García F, González-King H, Garcia NA, Peiró-Molina E, Sepúlveda P. 2018. Extracellular vesicles secreted by hypoxic AC10 cardiomyocytes modulate fibroblast cell motility. Frontiers in Cardiovascular Medicine 5:152. DOI: 10.3389/fcvm.2018.00152.
Park JE, Dutta B, Tse SW, Gupta N, Tan CF, Low JK, Yeoh KW, Kon OL, Tam JP, Sze SK. 2019. Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift. Oncogene 38:5158–5173. DOI: 10.1038/s41388-019-0782-x.
Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, Sze SK. 2010. Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Molecular & Cellular Proteomics 9:1085–1099. DOI: 10.1074/mcp.M900381-MCP200.
Ramteke A, Ting H, Agarwal C, Mateen S, Somasagara R, Hussain A, Graner M, Frederick B, Agarwal R, Deep G. 2015. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Molecular Carcinogenesis 54:554–565. DOI: 10.1002/mc.22124.
Riis S, Stensballe A, Emmersen J, Pennisi CP, Birkelund S, Zachar V, Fink T. 2016. Mass spectrometry analysis of adipose-derived stem cells reveals a significant effect of hypoxia on pathways regulating extracellular matrix. Stem Cell Research & Therapy 7:1–14. DOI: 10.1186/s13287-016-0310-7.
Salomon C, Kobayashi M, Ashman K, Sobrevia L, Mitchell MD, Rice GE. 2013a. Hypoxia-induced changes in the bioactivity of cytotrophoblast-derived exosomes. PLOS One 8:e79636. DOI: 10.1371/journal.pone.0079636.
Salomon C, Ryan J, Sobrevia L, Kobayashi M, Ashman K, Mitchell M, Rice GE. 2013b. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis. PLOS One 8:e68451. DOI: 10.1371/journal.pone.0068451.
Yoon JH, Kim J, Kim KL, Kim D-H, Jung S-J, Lee H, Ghim J, Kim D, Park JB, Ryu SH, Lee TG. 2014. Proteomic analysis of hypoxia-induced U373MG glioma secretome reveals novel hypoxia-dependent migration factors. Proteomics 14:1494–1502. DOI: 10.1002/pmic.201300554.