Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance

Hida, Kyoko; Maishi, Nako; Akiyama, Kosuke; Ohmura-Kakutani, Hitomi; Torii, Chisaho; Ohga, Noritaka; Osawa, Takahiro; Kojima, Hiroshi; Morimoto, Hirofumi; Morimoto, Masahiro; Shindoh, Masanobu; Shinohara, Nobuo

doi:10.1111/cas.13388

Cited by 44 publications

(45 citation statements)

References 29 publications

(72 reference statements)

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“…TECs are not only involved in the angiogenesis process to support primary tumor growth, but also promote tumor progression, metastasis and drug resistance [41]. TECs contain stem cell-like populations and overexpress MDR1 and aldehyde dehydrogenase (ALDH) and become resistant to chemotherapeutics such as paclitaxel and 5-fluorouracil in vitro [43,44].…”

Section: Tumor Endothelial Cells (Tecs)mentioning

confidence: 99%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

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Section: Tumor Endothelial Cells (Tecs)mentioning

confidence: 99%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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“…A new study showed that targeted elimination of macrophages elicited a type I interferon response in the tumor milieu that enhances the efficacy of platinum, but not taxane-based chemotherapy, underlining complicated regulatory roles for macrophages in chemotherapy-treated tumors [67]. TECs with high aldehyde dehydrogenase activity showed drug resistance [68]. TECs and TAMs can play key roles in drug resistance inasmuch as these tumorassociated cells often express drug resistance genes [69][70][71][72][73][74].…”

Section: Stromal Signal-driven Tumor Progressionmentioning

confidence: 99%

Exosome Release of Drugs: Coupling with Epithelial-Mesenchymal Transition

Eguchi¹,

Ono²,

Calderwood³

et al. 2019

Preprint

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Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

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“…High ALDH1 activity is also an in vitro and in vivo hallmark of CSCs. Patients with tumor cells with high ALDH1 levels often exhibit therapeutic resistance and have a poor prognosis [18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

Kim

Lee

Kim

et al. 2020

Preprint

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Cancer stem cells (CSCs) are regarded as essential targets to overcome tumor progression and therapeutic resistance; however, practical targeting approaches are limited. Here, we identify testis-specific Y-like protein 5 (TSPYL5) as a CSC-associated factor that promotes stemness and epithelial-to-mesenchymal transition in therapy-resistant non-small cell lung cancer (NSCLC) cells. Aberrantly activated PI3K/AKT pathway in therapy-resistant NSCLC cells promotes TSPYL5 phosphorylation at threonine-120 (pT120), which inhibits ubiquitination and stabilizes TSPYL5. TSPYL5 pT120 also supports SUMOylation, which leads to its nuclear translocation and functions as a transcriptional repressor of PTEN. Nuclear TSPYL5 also activates the transcription of CSC-associated genes, ALDH1 and CD44. Collectively, TSPYL5 pT120 maintains persistent CSC-like characteristics via transcriptional activation of CSC-associated genes and via a positive-feedback loop between the AKT/TSPYL5/PTEN and PTEN/PI3K/AKT signaling pathways. However, inhibition of TSPYL5 pT120 can block aberrant AKT/TSPYL5/PTEN cyclic signaling and cancer stemness. Our study suggests TSPYL5 as a novel target for cancer therapy.

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Tumor endothelial cells with high aldehyde dehydrogenase activity show drug resistance

Cited by 44 publications

References 29 publications

Tumor microenvironment complexity and therapeutic implications at a glance

Tumor microenvironment complexity and therapeutic implications at a glance

Exosome Release of Drugs: Coupling with Epithelial-Mesenchymal Transition

Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

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