Inhibition of tumor growth by mouse ROR1 specific antibody in a syngeneic mouse tumor model

Hassannia, Hadi; Amiri, Mohammad Mehdi; Jadidi‐Niaragh, Farhad; Hosseini-Ghatar, Reza; Khoshnoodi, Jalal; Sharifian, Roxana; Golsaz‐Shirazi, Forough; Jeddi‐Tehrani, Mahmood; Shokri, Fazel

doi:10.1016/j.imlet.2017.11.010

Cited by 18 publications

(13 citation statements)

References 21 publications

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“…Sections were then scanned using a digital slide scanner (Panoramic DESK, 3D Histech, Hungary). Evaluation of the microvessel density (MVD) was performed based on the previous report (Hassannia et al, 2017). Briefly, the sections were analyzed with two different magnifications (40× and 400×).…”

Section: Histopathologic Analysismentioning

confidence: 99%

Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Ghalamfarsa

Rastegari

Atyabi

et al. 2018

Journal Cellular Physiology

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CD73 facilitates tumor growth by upregulation of the adenosine (immunosuppressive factor) in the tumor microenvironment, however, its precise molecular mechanisms is not precisely understood. Regarding the importance of angiogenesis in tumor development and spreading, we decided to assign the anti-angiogenic effects of CD73 suppression. We used chitosan lactate (ChLa) nanoparticles (NPs) to deliver CD73-specific small interfering RNA (siRNA) into cancer cells. Our results showed that treatment of the 4T1 cells with CD73-specific siRNA-loaded NPs led to potent inhibition of cancer cell proliferation and cell cycle arrest, in vitro. This growth arrest was correlated with downregulation of angiogenesis-related molecules including vascular endothelial growth factor (VEGF)-A, VEGF-R2, interleukin (IL)-6, and transforming growth factor (TGF)-β. Moreover, administration of NPs loaded with CD73-siRNA into 4T1 breast cancer-bearing mice led to tumor regression and increased mice survival time accompanied with downregulation of angiogenesis (VEGF-A, VEGF-R2, VE-Cadherin, and CD31) and lymphangiogenesis (VEGF-C and LYVE-1)-related genes in the tumor site. Furthermore, the expression of angiogenesis promoting factors including IL-6, TGF-β, signal transducer, and activator of transcription (STAT)3, hypoxia inducible factor (HIF)-1α, and cyclooxygenase (COX)2 was decreased after the CD73 suppression in mice. Moreover, analysis of leukocytes derived from the tumor samples, spleen, and regional lymph nodes showed that they had lower capability for secretion of angiogenesis promoting factors after CD73-silencing. These results indicate that suppression of tumor development by downregulation of CD73 is in part related to angiogenesis arrest. These findings imply a promising strategy for inhibiting tumor growth accompanied with suppressing the angiogenesis process.

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Section: Histopathologic Analysismentioning

confidence: 99%

Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Ghalamfarsa

Rastegari

Atyabi

et al. 2018

Journal Cellular Physiology

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“…In addition to cirmtuzumab, a number of other anti-ROR1 therapies are also in pre-clinical development Ca, cancer; CLL, chronic lymphocytic leukaemia; Endo, endometrial; met, metastatic; SC, squamous cell; TNBC, triple-negative breast cancer. (Hojjat-Farsangi et al 2017, Yin et al 2017, Hassannia et al 2018. Of these, ROR1 chimeric antigen receptor (CAR)-T cell therapy has attracted interest.…”

Section: :12mentioning

confidence: 99%

An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target

Coopes

Henry

Llamosas

et al. 2018

Endocrine-Related Cancer

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Endometrial cancer is the most common gynaecological malignancy in developed nations, and its prevalence is rising as women defer or decide not to have children and as obesity rises, both key risk factors. Despite this, treatment options remain limited, particularly for advanced or refractory disease. New genomic analyses have revealed distinct mutational profiles with therapeutic and prognostic potential. Wnt signalling, which is pivotal in embryogenesis, healing and homeostasis, is of importance in the endometrium and has been linked to carcinogenesis. This review aims to update and discuss the current evidence for the role of β-catenin dependent and independent Wnt signalling, including the ROR receptors in the endometrium and its potential as a therapeutic target, in light of recent trials of Wnt-targeted therapy in multiple tumour types.

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“…Recent clinical strategies have focused on the direct targeting of ROR1 using monoclonal antibodies (mAbs). Many ROR1 mAbs have been designed and demonstrate significant preclinical efficacy [35,36,37]; cirmtuzumab (UC-951) [38] is currently in phase I–II of clinical trials for CLL and breast cancer. Encouraging preclinical studies suggest that the concomitant suppression of ROR1 and other oncogenic pathways may be helpful in attaining greater clinical benefits [13,20,39,40].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways

Karvonen

Barker

Kaleva

et al. 2019

Cells

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Signaling via the Wnt-related receptor tyrosine kinase-like orphan receptor 1 (ROR1) triggers tumorigenic features associated with cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT), while aberrant expression of ROR1 is strongly linked to advanced disease progression and chemoresistance. Several recent studies have shown that Wnt5a binding to ROR1 promotes oncogenic signaling by activating multiple pathways such as RhoA/Rac1 GTPases and PI3K/AKT, which in turn could induce transcriptional coactivator YAP/TAZ or polycomb complex protein BMI-1 signaling, respectively, to sustain stemness, metastasis and ultimately drug-resistance. These data point towards a new feedback loop during cancer development, linking Wnt5a-ROR1 signaling activation to YAP/TAZ or BMI-1 upregulation that could play an important role in disease progression and treatment resistance. This review focuses on the crosstalk between Wnt5a-ROR1 and YAP/TAZ or the BMI-1 signaling network, together with the current advancements in targeted strategies for ROR1-positive cancers.

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Inhibition of tumor growth by mouse ROR1 specific antibody in a syngeneic mouse tumor model

Cited by 18 publications

References 21 publications

Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

Anti‐angiogenic effects of CD73‐specific siRNA‐loaded nanoparticles in breast cancer‐bearing mice

An update of Wnt signalling in endometrial cancer and its potential as a therapeutic target

Molecular Mechanisms Associated with ROR1-Mediated Drug Resistance: Crosstalk with Hippo-YAP/TAZ and BMI-1 Pathways

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