Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

Farooqı, Ammad Ahmad; Fayyaz, Sundas; Qureshi, Muhammad Zahid; Rashid, Sadia

doi:10.1007/s00005-012-0169-y

Cited by 5 publications

(3 citation statements)

References 38 publications

(36 reference statements)

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“…Therefore, a lower expression of NKG2D ligand 2 on the surface of cancer cells favors their survival by reducing their chance of being recognized by NK cells. Many studies have focused on triggering the cell surface expression of NKG2D ligands on tumor cells as a potential therapeutic strategy for PCa [30–32]. Recently, it was reported that the knockdown of IL-6 in castration-resistant PCa cells rendered them more susceptible than control cells to NK cell-mediated cytotoxicity owing to an increased cell surface expression of NKG2D ligands [33].…”

Section: Discussionmentioning

confidence: 99%

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

Jeon

Kwon

et al. 2019

PLoS ONE

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Prostate cancer (PCa) is the most common cancer among men worldwide. Most PCa cases are not fatal; however, the outlook is poor when PCa spreads to another organ. Bone is the target organ in about 80% of patients who experience metastasis from a primary PCa tumor. In the present study, we characterized the secretome of PC3/nKR cells, which are a new subline of PC3 cells that were originally isolated from nude mice that were implanted with PC3 cells without anti-natural killer (NK) cell treatment. Wound healing and Transwell assays revealed that PC3/nKR cells had increased migratory and invasive activities in addition to a higher resistance to NK cells-induced cytotoxicity as compared to PC3 cells. We quantitatively profiled the secreted proteins of PC3/nKR and PC3 cells by liquid chromatography-tandem mass spectrometry analysis coupled with 2-plex tandem mass tag labeling. In total, 598 secretory proteins were identified, and 561 proteins were quantified, among which 45 proteins were secreted more and 40 proteins were secreted less by PC3/nKR cells than by PC3 cells. For validation, the adapter molecule crk, serpin B3, and cystatin-M were analyzed by western blotting. PC3/nKR cells showed the selective secretion of NKG2D ligand 2, HLA-A, and IL-6, which may contribute to their NK cell-mediated cytotoxicity resistance, and had a high secretion of crk protein, which may contribute to their high migration and invasion properties. Based on our secretome analysis, we propose that PC3/nKR cells represent a new cell system for studying the metastasis and progression of PCa.

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Section: Discussionmentioning

confidence: 99%

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

Jeon

Kwon

et al. 2019

PLoS ONE

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“…This allows for a mechanismand hypothesis-free exploration of potential drug interactions and, furthermore, makes possible the discovery of more complex and nuanced drug-target interactions [42,43]. This also opens the door for novel approaches, such as phage antimicrobials [63], immune system reprogramming [64] and regenerative medicine [65]. Additionally, predictive bioanalytical tools could also make use of vast data sets of biomedical data, enhancing the repurposing of drugs already approved by the FDA for human use.…”

Section: Translating Atomic-level Mechanistic Understanding To Personmentioning

confidence: 99%

CANDO and the infinite drug discovery frontier

Minie

Chopra

Sethi

et al. 2014

Drug Discovery Today

170

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The Computational Analysis of Novel Drug Opportunities (CANDO) platform (http://protinfo.org/cando) uses similarity of compound–proteome interaction signatures to infer homology of compound/drug behavior. We constructed interaction signatures for 3733 human ingestible compounds covering 48,278 protein structures mapping to 2030 indications based on basic science methodologies to predict and analyze protein structure, function, and interactions developed by us and others. Our signature comparison and ranking approach yielded benchmarking accuracies of 12–25% for 1439 indications with at least two approved compounds. We prospectively validated 49/82 ‘high value’ predictions from nine studies covering seven indications, with comparable or better activity to existing drugs, which serve as novel repurposed therapeutics. Our approach may be generalized to compounds beyond those approved by the FDA, and can also consider mutations in protein structures to enable personalization. Our platform provides a holistic multiscale modeling framework of complex atomic, molecular, and physiological systems with broader applications in medicine and engineering.

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“…Taken together, given exploiting NK cells as a therapeutic strategy for prostate cancer, which has shown promising bene ts in preclinical studies [44], our ndings demonstrated pterostilbene-treated prostate cancer cells enhanced their susceptibility to NK cell-mediated cytotoxicity with promoted IFN-γ and 107a, providing additional evidence for improving NK cell-based immunotherapeutic interventions against prostate cancer.…”

Section: Discussionmentioning

confidence: 64%

Inhibition of MiR-20a by Pterostilbene Facilitates Prostate Cancer Cells Killed by NK Cells Via up-Regulation of NKG2D Ligands and Down-Regulation of TGF-β1

Liang

Kang

et al. 2021

Preprint

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Purpose-Natural killer (NK) cells play a potent role in antitumor immunity via spontaneously eliminating tumor directly. However, some tumors such as prostate cancer constantly escape this immune response by down-regulating cell surface molecule recognition and/or secreting immune impressive cytokines. Pterostilbene, a dietary compound primarily found in blueberries, exhibits a potential anti-tumor activities and immunoregulation function. However, whether it could affect NK cells immune response against prostate cancer is not clear.Methods-NK cell cytotoxicity against prostate cancer cells was analyzed using the CytoTox 96 cytotoxicity assay kit. Flow cytometry was used to detected NK cell degranulation, NK cell-surface and intracellular protein expression. The effects of pterostilbene on TGF-β1 secretion were determined by Enzyme-linked immunosorbent assay. The candidate target gene of miR-20a was determined by luciferase reporter assay and the expression of major histocompatibility complex class I chain-related proteins A and B (MICA/B) was detected by quantitative real-time polymerase chain reaction.Results-We found pterostilbene could enhance expression of MICA/B on prostate cancer cells surface, which are ligands of the natural killer group 2 member D (NKG2D) expressed by NK cells, and inhibit TGF-β1 secretion by prostate cancer cells. Further, we discovered that these effects were caused by inhibition of miR-20a in prostate cancer cells by pterostilbene. MiR-20a could target the 3’ untranslated region (UTR) of MICA/B, resulting in their expression down-regulation. Inhibition of TGF-β1 function by its specific antibody attenuated its impairment to NKG2D on NK cells. Finally, we observed that pterostilbene-treated prostate cancer cells were more easily to be killed by NK cells.Conclusions-Our findings demonstrated inhibition of miR-20a by pterostilbene in prostate cancer cells could increase MICA/B expression and decrease TGF-β1 secretion, which enhanced NK cell-mediated cytotoxicity againt prostate cancer cells, suggesting a potential approach for increasing anti-prostate cancer immune.

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Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

Cited by 5 publications

References 38 publications

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

Secretome profiling of PC3/nKR cells, a novel highly migrating prostate cancer subline derived from PC3 cells

CANDO and the infinite drug discovery frontier

Inhibition of MiR-20a by Pterostilbene Facilitates Prostate Cancer Cells Killed by NK Cells Via up-Regulation of NKG2D Ligands and Down-Regulation of TGF-β1

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