Breast cancer: insights in disease and influence of drug methotrexate

Yang, Vítor; Gouveia, Maria João; Santos, Joana; Koksch, Beate; Amorim, Irina; Gärtner, Fátima; Vale, Nuno

doi:10.1039/d0md00051e

Cited by 46 publications

(25 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This allowed us to establish a mechanistic proof of principle linking miR-146 to at least one of the phenotypic properties of CSCs, i.e., drug resistance, in particular resistance to MTX, a chemotherapy agent and immune system suppressant, widely used for the treatment of a variety of cancers, including advanced-stage BC ( Yang et al, 2020b ). The genetic interaction between miR-146 and MTX has been revealed as highly effective both in vitro and in vivo and further supported by the regulation of the enzymes of the folate biosynthetic pathway by miR-146 observed in the transcriptomic analyses.…”

Section: Discussionmentioning

confidence: 99%

miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer

Tordonato

Marzi

Giangreco

et al. 2021

Journal of Cell Biology

View full text Add to dashboard Cite

Although ectopic overexpression of miRNAs can influence mammary normal and cancer stem cells (SCs/CSCs), their physiological relevance remains uncertain. Here, we show that miR-146 is relevant for SC/CSC activity. MiR-146a/b expression is high in SCs/CSCs from human/mouse primary mammary tissues, correlates with the basal-like breast cancer subtype, which typically has a high CSC content, and specifically distinguishes cells with SC/CSC identity. Loss of miR-146 reduces SC/CSC self-renewal in vitro and compromises patient-derived xenograft tumor growth in vivo, decreasing the number of tumor-initiating cells, thus supporting its pro-oncogenic function. Transcriptional analysis in mammary SC-like cells revealed that miR-146 has pleiotropic effects, reducing adaptive response mechanisms and activating the exit from quiescent state, through a complex network of finely regulated miRNA targets related to quiescence, transcription, and one-carbon pool metabolism. Consistent with these findings, SCs/CSCs display innate resistance to anti-folate chemotherapies either in vitro or in vivo that can be reversed by miR-146 depletion, unmasking a “hidden vulnerability” exploitable for the development of anti-CSC therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer

Tordonato

Marzi

Giangreco

et al. 2021

Journal of Cell Biology

View full text Add to dashboard Cite

show abstract

“…Methotrexate (MTX) was considered after a thorough analysis of the literature. Methotrexate (MTX) is a drug used to combat cancers such as non-small cell lung cancer, breast cancer, and ovarian cancer [23]. However, only a few experiments have been triggered to treat GBM with PLGA solid lipid nanoparticles filled with methotrexate (MTX) [24].…”

Section: In-vitro Investigation Of Polymeric Lipid Hybrid Nanoparticles (Plhns) Of a Chemotherapeutic Drug For The Treatment Of Glioblastmentioning

confidence: 99%

In-vitro Investigation of Polymeric Lipid Hybrid Nanoparticles (Plhns) Of a Chemotherapeutic Drug for the Treatment of Glioblastoma Multiforme

Bhattacharya¹

2021

Preprint

View full text Add to dashboard Cite

PHLNs (polymeric lipid hybrid nanoparticles) are core–shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) & glyceryl tripalmitate prepared using solvent injection & homogenization method for glioblastoma treatment option. The MTX loaded PLHNPs optimized by Box–Behnken design to minimize particle size, higher entrapment efficacy, and maximize MTX concentration in the brain at 4h. The particle size, entrapment efficacy, concentration of drug in brain at 4h, zeta potential and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51-233.37nm, 70.56-86.34%, 6.38-12.38 μg/mL, 25.78-36.31mV & 1.02-5.32. in-vitro drug release studies, cellular internalization of optimized formulation against U-87 MG shows good anticancer effects.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Cancer is one of the major causes of morbidity and mortality worldwide [ 1 ]. Among the numerous different types of cancer, breast cancer is generally regarded as the most common malignancy, predominantly in female patients, and the second leading cause of cancer-related deaths in women around the world [ 1 , 2 ]. Among generally used remedies for breast cancer, including hormonal therapy, chemotherapy and surgery, radiotherapy remains a standard arm in the arsenal of oncologists in order to cope with this great challenge to women’s health, aiming at improving the prognosis of the disease [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of the Proteoglycan Decorin Fills in the Tumor-Promoting Phenotype of Ionizing Radiation-Induced Senescent Human Breast Stromal Fibroblasts

Mavrogonatou

Papadopoulou

Fotopoulou

et al. 2021

Cancers

View full text Add to dashboard Cite

Down-regulation of the small leucine-rich proteoglycan decorin in the stroma is considered a poor prognostic factor for breast cancer progression. Ionizing radiation, an established treatment for breast cancer, provokes the premature senescence of the adjacent to the tumor stromal fibroblasts. Here, we showed that senescent human breast stromal fibroblasts are characterized by the down-regulation of decorin at the mRNA and protein level, as well as by its decreased deposition in the pericellular extracellular matrix in vitro. Senescence-associated decorin down-regulation is a long-lasting process rather than an immediate response to γ-irradiation. Growth factors were demonstrated to participate in an autocrine manner in decorin down-regulation, with bFGF and VEGF being the critical mediators of the phenomenon. Autophagy inhibition by chloroquine reduced decorin mRNA levels, while autophagy activation using the mTOR inhibitor rapamycin enhanced decorin transcription. Interestingly, the secretome from a series of both untreated and irradiated human breast cancer cell lines with different molecular profiles inhibited decorin expression in young and senescent stromal fibroblasts, which was annulled by SU5402, a bFGF and VEGF inhibitor. The novel phenotypic trait of senescent human breast stromal fibroblasts revealed here is added to their already described cancer-promoting role via the formation of a tumor-permissive environment.

show abstract

Breast cancer: insights in disease and influence of drug methotrexate

Abstract: Methotrexate might be valuable to fight breast cancer.

Cited by 46 publications

References 147 publications

miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer

miR-146 connects stem cell identity with metabolism and pharmacological resistance in breast cancer

In-vitro Investigation of Polymeric Lipid Hybrid Nanoparticles (Plhns) Of a Chemotherapeutic Drug for the Treatment of Glioblastoma Multiforme

Down-Regulation of the Proteoglycan Decorin Fills in the Tumor-Promoting Phenotype of Ionizing Radiation-Induced Senescent Human Breast Stromal Fibroblasts

Contact Info

Product

Resources

About