scholarly journals Tumour endothelial cells acquire drug resistance in a tumour microenvironment

2013 ◽  
Vol 153 (3) ◽  
pp. 243-249 ◽  
Author(s):  
K. Hida ◽  
K. Akiyama ◽  
N. Ohga ◽  
N. Maishi ◽  
Y. Hida
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Tumour Microenvironment ◽  
Acquire Drug Resistance

scholarly journals Tumor Endothelial Cells Acquire Drug Resistance by MDR1 Up-Regulation via VEGF Signaling in Tumor Microenvironment

2012 ◽  
Vol 180 (3) ◽  
pp. 1283-1293 ◽  
Author(s):  
Kosuke Akiyama ◽  
Noritaka Ohga ◽  
Yasuhiro Hida ◽  
Taisuke Kawamoto ◽  
Yoshihiro Sadamoto ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Vegf Signaling ◽  
Tumor Endothelial Cells ◽  
Acquire Drug Resistance

scholarly journals Normoxic Tumour Extracellular Vesicles Modulate the Response of Hypoxic Cancer and Stromal Cells to Doxorubicin In Vitro

2020 ◽  
Vol 21 (17) ◽  
pp. 5951
Author(s):  
Laura Patras ◽  
Marcel H. A. M. Fens ◽  
Pieter Vader ◽  
Arjan Barendrecht ◽  
Alina Sesarman ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Extracellular Vesicles ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Tumour Microenvironment ◽  
Hypoxia Inducible Factor 1 ◽  
Apoptotic Protein ◽  
Donor Cells

Extracellular vesicles (EV) secreted in the tumour microenvironment (TME) are emerging as major antagonists of anticancer therapies by orchestrating the therapeutic outcome through altering the behaviour of recipient cells. Recent evidence suggested that chemotherapeutic drugs could be responsible for the EV-mediated tumour–stroma crosstalk associated with cancer cell drug resistance. Here, we investigated the capacity of tumour EV (TEV) secreted by normoxic and hypoxic (1% oxygen) C26 cancer cells after doxorubicin (DOX) treatment to alter the response of naïve C26 cells and RAW 264.7 macrophages to DOX. We observed that C26 cells were less responsive to DOX treatment under normoxia compared to hypoxia, and a minimally cytotoxic DOX concentration that mounted distinct effects on cell viability was selected for TEV harvesting. Homotypic and heterotypic pretreatment of naïve hypoxic cancer and macrophage-like cells with normoxic DOX-elicited TEV rendered these cells slightly less responsive to DOX treatment. The observed effects were associated with strong hypoxia-inducible factor 1-alpha (HIF-1α) induction and B-cell lymphoma–extra-large anti-apoptotic protein (Bcl-xL)-mediated anti-apoptotic response in normoxic DOX-treated TEV donor cells, being also tightly connected to the DOX-TEV-mediated HIF-1α induction, as well as Bcl-xL levels increasing in recipient cells. Altogether, our results could open new perspectives for investigating the role of chemotherapy-elicited TEV in the colorectal cancer TME and their modulatory actions on promoting drug resistance.

scholarly journals Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 104 ◽  
Author(s):  
Hoi-Hin Kwok ◽  
Ziyu Ning ◽  
Peony Chong ◽  
Thomas Wan ◽  
Margaret Ng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Lung Adenocarcinoma ◽  
Kinase Inhibitor ◽  
Quantitative Polymerase Chain Reaction ◽  
Tumour Microenvironment ◽  
Extracellular Vesicle ◽  
Drug Resistant ◽  
Anaplastic Lymphoma ◽  
Tki Treatment

Anaplastic lymphoma kinase (ALK) translocation is an actionable mutation in lung adenocarcinoma. Nonetheless tumour consists of heterogeneous cell subpopulations with diverse phenotypes and genotypes, and cancer cells can actively release extracellular vesicles (EVs) to modulate the phenotype of other cells in the tumour microenvironment. We hypothesized that EVs derived from a drug-resistant subpopulation of cells could induce drug resistance in recipient cells. We have established ALK-translocated lung adenocarcinoma cell lines and subclones. The subclones have been characterized and the expression of EV-RNAs determined by quantitative polymerase chain reaction. The effects of EV transfer on drug resistance were examined in vitro. Serum EV-RNA was assayed serially in two patients prescribed ALK-tyrosine kinase inhibitor (ALK-TKI) treatment. We demonstrated that the EVs from an ALK-TKI-resistant subclone could induce drug resistance in the originally sensitive subclone. EV-RNA profiling revealed that miRNAs miR-21-5p and miR-486-3p, and lncRNAs MEG3 and XIST were differentially expressed in the EVs secreted by the resistant subclones. These circulating EV-RNA levels have been found to correlate with disease progression of EML4-ALK-translocated lung adenocarcinoma in patients prescribed ALK-TKI treatment. The results from this study suggest that EVs released by a drug-resistant subpopulation can induce drug resistance in other subpopulations and may sustain intratumoural heterogeneity.

The mechanism of human angiosarcoma drug resistance

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9567-9567
Author(s):  
V. Ravi ◽  
D. Henry ◽  
S. Chen ◽  
M. K. Wong
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Malignant Neoplasm ◽  
Therapeutic Strategies ◽  
Migration And Invasion ◽  
Development Of Resistance ◽  
Vegf Pathway ◽  
And Function ◽  
Invasion Assays

9567 Background: Angiosarcoma (AS) is a malignant neoplasm of endothelial cells. AS has an extremely poor outcome since it can metastasize widely and rapidly becomes chemoresistant. Understanding the mechanism of this resistance is important not only because of the critical need for new therapeutic strategies in sarcoma, but also since it sheds light on important pathways in endothelial growth that may help understand tumor angiogenesis. Methods/Results: We have established and characterized stable pre-chemotherapy (named B8) and chemotherapy-resistant (named D3) angiosarcoma cell lines from an individual patient with primary (non radiated) breast angiosarcoma prior to initiation of chemotherapy and later after development of resistance to adriamycin, ifosfamide, gemcitabine, docetaxel, paclitaxel, interferon, thalidomide and bevacizumab. D3 cells differ dramatically from B8s in morphology and function. Prechemotherapy B8 cells assume a polygonal morphology reminiscent of native endothelial cells, the D3 cells throw out long processes that span several cell lengths, and do not appear to contact-inhibit. Migration and invasion assays confirm the highly motile nature of these cells. Although it is not surprising that the D3 cells were doxorubicin resistant, we found that unlike the B8 cells, the D3 cells actively transcribe VEGF. In keeping with this, D3 cells are relatively more sensitive to growth inhibition by the anti-VEGF drug bevacizumab than chemonaïve B8 cells. Conclusion: These studies reveal two avenues to target chemoresistant human angiosarcoma; via agents affecting cell migration and those agents that target the VEGF pathway. No significant financial relationships to disclose.

Antiproliferative, antiangiogenesis, and reversal of chemoresistance by specific cathepsin L inhibitors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14643-e14643
Author(s):  
A. Rebbaa ◽  
E. Dyskin ◽  
E. Dier ◽  
C. Gallati ◽  
C. Honko ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Tumor Growth ◽  
Anticancer Agents ◽  
Cellular Proliferation ◽  
Cathepsin L ◽  
Neuroblastoma Cell ◽  
Drug Candidate ◽  
Dependent Manner

e14643 Background: Uncontrolled proliferation, enhanced angiogenesis and the development of resistance to therapy are hallmarks of cancer; therefore, the development of approaches to simultaneously target these three processes would be the most desirable. Previous work from our laboratory has demonstrated that NapSul-Ile-Trp-CHO (NSITC), a specific inhibitors of cathepsin L, and its analogs strongly inhibited cancer cell proliferation and suppressed the development of drug resistance in vitro (Zheng X. et al., 2004 Cancer Res. 64:1773–80). In the present study, we sought to investigate the validity of these observations in vivo, and to dissect the underlying mechanism(s). Methods: Nude mice (Strain CD1) bearing xenografts of doxorubicin resistant neuroblastoma cell line SKN-SH/R were challenged with doxorubicin (1.5 mg/Kg) alone, NSITC (20 mg/kg) alone or the combination of both. The effect of NSITC on tumor angiogenesis was also investigated using the Chick Chorioallantoic Membrane (CAM). Putative mechanisms by which NSITC inhibits cellular proliferation, drug resistance and angiogenesis were studied using cancer and endothelial cells maintained in culture. Results: The in vivo data indicated that doxorubicin alone had no effect on tumor growth, however NSITC alone exerted 40% inhibition and the combination of both drugs reduced tumor growth by about 90%. NSITC also caused a 125% inhibition of blood vessel branching in the CAM model (at 1 μg/CAM). Investigation of the underlying mechanisms of its action revealed that at low concentration, NSITC forces cancer cells into senescence, preventing them from developing resistance to classical anticancer agents, and at high concentrations, it induced autophagic cell death. NSITC also strongly inhibited the proliferation and invasion of endothelial cells in a dose dependent manner with more than 90% inhibition at 20 μM. Conclusions: Overall, these findings suggest that NSITC has multi-anticancer functions and thus, may represent a potential drug candidate for the treatment of aggressive malignancies. No significant financial relationships to disclose.

scholarly journals HIF-1α of Bone Marrow Endothelial Cells Implies Relapse and Drug Resistance in Patients with Multiple Myeloma and May Act as a Therapeutic Target

2013 ◽  
Vol 20 (4) ◽  
pp. 847-858 ◽  
Author(s):  
Roberto Ria ◽  
Ivana Catacchio ◽  
Simona Berardi ◽  
Annunziata De Luisi ◽  
Antonella Caivano ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Endothelial Cells ◽  
Therapeutic Target

scholarly journals Cross-drug resistance to sunitinib induced by doxorubicin in endothelial cells

2014 ◽  
Vol 9 (3) ◽  
pp. 1287-1292 ◽  
Author(s):  
LIMIN HUANG ◽  
CHAOQUAN HU ◽  
MÉLANIE DI BENEDETTO ◽  
RÉMI VARIN ◽  
JIELIN LIU ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells
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