cRGD-functionalized nanoparticles for combination therapy of anti-endothelium dependent vessels and anti-vasculogenic mimicry to inhibit the proliferation of ovarian cancer

Wang, Yifeng; Lin, Tong; Wang, Jianguo; Luo, Jiamao; Tang, Jiao; Zhong, Lijuan; Xiao, Qian; Niu, Wenbo; Li, Jin‐Heng; Zhu, Junqiao; Chen, Huajian; Li, Xin; Wang, Ying

doi:10.1016/j.actbio.2019.06.039

Cited by 39 publications

(19 citation statements)

References 30 publications

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“…In recent years, studies have found a novel tumor blood supply pattern, called vasculogenic mimicry (VM), which occurs in certain highly aggressive malignancies, and is closely related to poor clinical results and poor prognosis [18][19][20][21]. It has become one of the potential targets for anticancer therapy [22][23][24][25]. We previously reported that VM exists in GBC and is associated with the patient's poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

Pan

Wang

Ansari

et al. 2020

J Exp Clin Cancer Res

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Background Cancer-associated fibroblasts (CAFs) and vasculogenic mimicry (VM) play important roles in the occurrence and development of tumors. However, the relationship between CAFs and VM formation, especially in gallbladder cancer (GBC) has not been clarified. In this study, we investigated whether gallbladder CAFs (GCAFs) can promote VM formation and tumor growth and explored the underlying molecular mechanism. Methods A co-culture system of human GBC cells and fibroblasts or HUVECs was established. VM formation, proliferation, invasion, migration, tube formation assays, CD31-PAS double staining, optic/electron microscopy and tumor xenograft assay were used to detect VM formation and malignant phenotypes of 3-D co-culture matrices in vitro, as well as the VM formation and tumor growth of xenografts in vivo, respectively. Microarray analysis was used to analyze gene expression profile in GCAFs/NFs and VM (+)/VM (−) in vitro. QRT-PCR, western blotting, IHC and CIF were used to detected NOX4 expression in GCAFs/NFs, 3-D culture/co-culture matrices in vitro, the xenografts in vivo and human gallbladder tissue/stroma samples. The correlation between NOX4 expression and clinicopathological and prognostic factors of GBC patients was analyzed. And, the underlying molecular mechanism of GCAFs promoting VM formation and tumor growth in GBC was explored. Results GCAFs promote VM formation and tumor growth in GBC; and the finding was confirmed by facts that GCAFs induced proliferation, invasion, migration and tube formation of GBC cells in vitro, and promoted VM formation and tumor growth of xenografts in vivo. NOX4 is highly expressed in GBC and its stroma, which is the key gene for VM formation, and is correlated with tumor aggression and survival of GBC patients. The GBC patients with high NOX4 expression in tumor cells and stroma have a poor prognosis. The underlying molecular mechanism may be related to the upregulation of NOX4 expression through paracrine IL-6 mediated IL-6/JAK/STAT3 signaling pathway. Conclusions GCAFs promote VM formation and tumor growth in GBC via upregulating NOX4 expression through the activation of IL-6-JAK-STAT3 signal pathway. NOX4, as a VM-related gene in GBC, is overexpressed in GBC cells and GCAFs, which is related to aggression and unfavorable prognosis of GBC patients.

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Section: Introductionmentioning

confidence: 99%

Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

Pan

Wang

Ansari

et al. 2020

J Exp Clin Cancer Res

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“…However, it is easy to acquire drug resistance, resulting in poor effects in their actual clinical application [234]. Bevacizumab is reported to activate the PI3K-AKT pathway through autophagy-induced ROS to promote kinase domain insertion receptor (KDR) phosphorylation in [228,229], [230] Verteporfin YAP, TEAD Ang2, MMP2, VE-cadherin, α-SMA Inhibition Inhibition [231,232] cRGD-functionalized nanoparticles α v β 3 inhibition inhibition [233] GSC, and to activate KDR/VEGFR-2 to induce stem cell transformation to endothelial cell-like phenotypes, resulting in VM [206]. Further evidence suggests that activation of the IL-8-CXCR2 pathway is responsible for development of resistance to traditional anti-angiogenic therapies in glioblastoma cells and the development of VM [235].…”

Section: Angiogenesis Inhibitormentioning

confidence: 99%

“…For example, treatment with a thrombin inhibitor targeting VM, such as r-Hirudin and DTIP, has shown obvious inhibitory effects on tumor angiogenesis [212]. The latest research has focused on the use of integrin αvβ3 and self-assembly engineering to prepare nanoparticletargeted drugs that can inhibit endothelial sprouting angiogenesis and VM with significant effects [233].…”

Section: Angiogenesis and Vasculogenic Mimicry Inhibitorsmentioning

confidence: 99%

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

et al. 2021

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Background Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil “microenvironment” for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. Main body In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. Conclusion Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

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“…The term VM means that cancer cells mimic endothelial cells, which results in the formation of vessel-like structures that supply growth factors and oxygen [35]. Wang et al [31] prepared cRGD-conjugated heparin, which acts as a therapeutic against VM and conjugation of the ligand backbone. They demonstrated that the cRGD-conjugated heparin efficiently inhibited tube formation in an in vitro study and inhibited tumor growth in ovarian cancer-bearing mice by suppressing VM formation.…”

Section: For Targeting Tumor Endothelial Cellsmentioning

confidence: 99%

Targeting Tumor Endothelial Cells with Nanoparticles

Sakurai

Akita

Harashima

2019

IJMS

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Because angiogenesis is a major contributor to cancer progression and metastasis, it is an attractive target for cancer therapy. Although a diverse number of small compounds for anti-angiogenic therapy have been developed, severe adverse effects commonly occur, since small compounds can affect not only tumor endothelial cells (TECs), but also normal endothelial cells. This low selectivity for TECs has motivated researchers to develop alternate types of drug delivery systems (DDSs). In this review, we summarize the current state of knowledge concerning the delivery of nano DDSs to TECs. Their payloads range from small compounds to nucleic acids. Perspectives regarding new therapeutic targets are also mentioned.

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cRGD-functionalized nanoparticles for combination therapy of anti-endothelium dependent vessels and anti-vasculogenic mimicry to inhibit the proliferation of ovarian cancer

Cited by 39 publications

References 30 publications

Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

Targeting Tumor Endothelial Cells with Nanoparticles

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