Kavanagh, E. L.; Lindsay, S.; Halasz, M.; Gubbins, L. C.; Weiner-Gorzel, K.; Guang, M. H. Z.; McGoldrick, A.; Collins, E.; Henry, M.; Blanco-Fernandez, A.; Gorman, P. O.; Fitzpatrick, P.; Higgins, M. J.; Dowling, P.; McCann, A. published the artcile< Protein and chemotherapy profiling of extracellular vesicles harvested from therapeutic induced senescent triple negative breast cancer cells>, Related Products of 6823-69-4, the main research area is chemotherapy extracellular vesicle therapeutic induced senescent breast cancer.
Triple neg. breast cancer (TNBC) is an aggressive subtype with relatively poor clin. outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemo resistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. TIS was induced and confirmed in Cal51 TNBC cells using the chemotherapeutic paclitaxel (PTX) (Taxol). Mass spectrometry (MS) anal. of EVs harvested from TIS compared with control Cal51 cells was performed using Ingenuity Pathway Anal. and InnateDB programs. We demonstrate that TIS Cal51 cells treated with 75 nm PTX for 7 days became senescent (senescence-associated β-galactosidase (SA-β-Gal) pos., Ki67-neg., increased p21 and p16, G2/M cell cycle arrest) and released significantly more EVs (P = 0.0002) and exosomes (P = 0.0007) than non-senescent control cells. Moreover, TIS cells displayed an increased expression of the multidrug resistance protein 1/p-glycoprotein. MS anal. demonstrated that EVs derived from senescent Cal51 cells contained 142 proteins with a significant increased fold change compared with control EVs. Key proteins included ATPases, annexins, tubulins, integrins, Rabs and insoluble senescence-associated secretory phenotype (SASP) factors. A fluorescent analog of PTX (Flutax-2) allowed appreciation of the removal of chemotherapy in EVs from senescent cells. Treatment of TIS cells with the exosome biogenesis inhibitor GW4869 resulted in reduced SA-β-Gal staining (P = 0.04). In summary, this study demonstrates that TIS cells release significantly more EVs compared with control cells, containing chemotherapy and key proteins involved in cell proliferation, ATP depletion, apoptosis and the SASP. These findings may partially explain why cancer senescent cells remain viable despite chemo therapeutic challenge.
Oncogenesis published new progress about Annexins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Related Products of 6823-69-4.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem