Supramolecular magnetonanohybrids for multimodal targeted therapy of triple-negative breast cancer cells

2020 ◽  
Vol 8 (32) ◽  
pp. 7166-7188 ◽  
Author(s):  
Alexandra A. P. Mansur ◽  
Herman S. Mansur ◽  
Alice G. Leonel ◽  
Isadora C. Carvalho ◽  
Manuela C. G. Lage ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative

All-in-one nanosoldier on a targeted mission: killing the triple-negative breast cancer cell enemy.

Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the differential diagnosis of Her-2 negative breast cancer

2016 ◽  
Vol 54 (4) ◽  
pp. 463-471 ◽  
Author(s):  
Praveenkumar Shetty ◽  
Vidya S Patil ◽  
Rajashekar Mohan ◽  
Leonard Clinton D’souza ◽  
Anil Bargale ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Critical Role ◽  
Autocrine Regulation ◽  
Her 2 ◽  
Positive Breast Cancer

Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model. Results Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P < 0.01) and Her-2 positive cases (217.75 ± 60.59 ng/mL, P < 0.0001). In Her-2 negative cases, the HB-EGF concentrations (179.16 ± 118.81 pg/mL) were highly significant compared with normal (14.92 ± 17.33 pg/mL, P < 0.001). IL-6 concentrations were increased significantly in both the breast cancer phenotypes as compared with normal ( P < 0.001). Conclusion The specific expression pattern of annexinA2 and HB-EGF in triple-negative breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.

scholarly journals Glucose-limiting conditions induce an invasive population of MDA-MB-231 breast cancer cells with increased connexin 43 expression and membrane localization

2021 ◽  
Vol 15 (2) ◽  
pp. 223-236
Author(s):  
Jennifer C. Jones ◽  
Amanda M. Miceli ◽  
Mary M. Chaudhry ◽  
Chloe S. Kaunitz ◽  
Mallika A. Jai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Nutrient Availability ◽  
Connexin 43 ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Low Glucose

AbstractGap junctional intercellular communication (GJIC) is a homeostatic process mediated by membrane channels composed of a protein family known as connexins. Alterations to channel activity can modulate suppression or facilitation of cancer progression. These varying roles are influenced by the cancer cell genetic profile and the context-dependent mechanisms of a dynamic extracellular environment that encompasses fluctuations to nutrient availability. To better explore the effects of altered cellular metabolism on GJIC in breast cancer, we generated a derivative of the triple-negative breast cancer cell line MDA-MB-231 optimized for growth in low-glucose. Reduced availability of glucose is commonly encountered during tumor development and leads to metabolic reprogramming in cancer cells. MDA-MB-231 low-glucose adapted cells exhibited a larger size with improved cell–cell contact and upregulation of cadherin-11. Additionally, increased protein levels of connexin 43 and greater plasma membrane localization were observed with a corresponding improvement in GJIC activity compared to the parental cell line. Since GJIC has been shown to affect cellular invasion in multiple cancer cell types, we evaluated the invasive qualities of these cells using multiple three-dimensional Matrigel growth models. Results of these experiments demonstrated a significantly more invasive phenotype. Moreover, a decrease in invasion was noted when GJIC was inhibited. Our results indicate a potential response of triple-negative breast cancer cells to reduced glucose availability that results in changes to GJIC and invasiveness. Delineation of this relationship may help elucidate mechanisms by which altered cancer cell metabolism affects GJIC and how cancer cells respond to nutrient availability in this regard.

scholarly journals Application of a Biphasic Mathematical Model of Cancer Cell Drug Response for Formulating Potent and Synergistic Targeted Drug Combinations to Triple Negative Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1087
Author(s):  
Jinyan Shen ◽  
Li Li ◽  
Niall G. Howlett ◽  
Paul S. Cohen ◽  
Gongqin Sun
Keyword(s):  
Breast Cancer ◽  
Mathematical Model ◽  
Targeted Therapy ◽  
Cancer Cells ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Drug Combinations ◽  
Targeted Drug

Triple negative breast cancer is a collection of heterogeneous breast cancers that are immunohistochemically negative for estrogen receptor, progesterone receptor, and ErbB2 (due to deletion or lack of amplification). No dominant proliferative driver has been identified for this type of cancer, and effective targeted therapy is lacking. In this study, we hypothesized that triple negative breast cancer cells are multi-driver cancer cells, and evaluated a biphasic mathematical model for identifying potent and synergistic drug combinations for multi-driver cancer cells. The responses of two triple negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, to a panel of targeted therapy drugs were determined over a broad range of concentrations. The analyses of the drug responses by the biphasic mathematical model revealed that both cell lines were indeed dependent on multiple drivers, and inhibitors of individual drivers caused a biphasic response: a target-specific partial inhibition at low nM concentrations, and an off-target toxicity at μM concentrations. We further demonstrated that combinations of drugs, targeting each driver, cause potent, synergistic, and cell-specific cell killing. Immunoblotting analysis of the effects of the individual drugs and drug combinations on the signaling pathways supports the above conclusion. These results support a multi-driver proliferation hypothesis for these triple negative breast cancer cells, and demonstrate the applicability of the biphasic mathematical model for identifying effective and synergistic targeted drug combinations for triple negative breast cancer cells.

scholarly journals Dual Targeted Therapy with p53 siRNA and Epigallocatechingallate in a Triple Negative Breast Cancer Cell Model

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0120936 ◽  
Author(s):  
Cornelia Braicu ◽  
Valentina Pileczki ◽  
Laura Pop ◽  
Roxana Cojocneanu Petric ◽  
Sergiu Chira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Model ◽  
Breast Cancer Cell Model

MiRNAs-181a/b as Predictive biomarkers for olaparib sensitivity in triple-negative breast cancer cells.

2017 ◽  
Vol 12 (1) ◽  
pp. 221-229
Author(s):  
Abeer M. Ashmawy ◽  
Mona A. Sheta ◽  
Faten Zahran ◽  
Abdel Hady A. Abdel Wahab
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Predictive Biomarkers
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