Sunitinib increases the cancer stem cells and vasculogenic mimicry formation via modulating the lncRNA-ECVSR/ERβ/Hif2-α signaling

Cancer stem cells (CSCs) refer to a subpopulation of cancer cells responsible for tumorigenesis, metastasis, and drug resistance. Increasing evidence suggests that CSC-associated tumor neovascularization partially contributes to the failure of cancer treatment. In this review, we discuss the roles of CSCs on tumor-associated angiogenesis via trans-differentiation or forming the capillary-like vasculogenic mimicry, as well as the roles of CSCs on facilitating endothelial cell-involved angiogenesis to support tumor progression and metastasis. Furthermore, we discuss the underlying regulation mechanisms, including the intrinsic signals of CSCs and the extrinsic signals such as cytokines from the tumor microenvironment. Further research is required to identify and verify some novel targets to develop efficient therapeutic approaches for more efficient cancer treatment through interfering CSC-mediated neovascularization.

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EBV latent membrane proteins promote hybrid epithelial-mesenchymal and extreme mesenchymal states of nasopharyngeal carcinoma cells for tumorigenicity

PLoS Pathogens ◽

10.1371/journal.ppat.1009873 ◽

2021 ◽

Vol 17 (8) ◽

pp. e1009873

Author(s):

Nannan Zhu ◽

Xiaoting Xu ◽

Yan Wang ◽

Musheng Zeng ◽

Yan Yuan

Keyword(s):

Stem Cells ◽

Nasopharyngeal Carcinoma ◽

Cancer Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Vasculogenic Mimicry ◽

Metastatic Potential ◽

Carcinoma Cells ◽

Tumor Xenograft ◽

Additional Function ◽

Mesenchymal Transition

EBV-encoded LMPs are consistently detected in nasopharyngeal carcinoma (NPC). Recent evidence suggests potential roles of LMP1 and LMP2A in Epithelial-to-mesenchymal transition (EMT) process in NPC. EMT engages in the generation and maintenance of cancer stem cells (CSCs) and confers on cancer cells increased tumor-initiating and metastatic potential, and higher resistance to anticancer therapies. However, how LMP1 and LMP2A regulate the EMT process to generate cells with different EMT states and its implications for tumor progression remain unclear. Here we report that LMP1 and LMP2A promote EMT that drives NPC cells from the epithelial-like state (CD104+, CD44low) to epithelial-mesenchymal hybrid (E/M) state (CD104+, CD44high). Furthermore, LMP2A possesses an additional function in stabilizing LMP1 and increasing the level of LMP1 in NPC cells. The elevated LMP1 further forces the EMT to generate extreme-mesenchymal (xM) state cells (CD104-, CD44high). To define the tumorigenic features of cancer stem cells at different states in the EMT spectrum, E, E/M and xM subpopulations were isolated and tested for tumorigenic capability in a tumor xenograft animal model. We found that the cells with E/M phenotypes possess the highest tumor initiating capacity. However, the xM subpopulation exhibits increased vasculogenic mimicry, a hallmark of metastatic cancers. Taken together, coordinated action of LMP1 and LMP2A generates an array of intermediate subpopulations in the EMT spectrum that are responsible for distinct tumorigenic features of NPC such as tumor-initiation, vasculogenesis, and metastasis.

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Crosstalks Among Cancer Stem Cells and Histopathologic Features in Determining Prognosis in Canine Mammary Gland Carcinomas

Acta veterinaria ◽

10.2478/acve-2021-0026 ◽

2021 ◽

Vol 71 (3) ◽

pp. 303-317

Author(s):

Havva Marzban ◽

Gelareh Chamani ◽

Fariba Khaki ◽

Parnian Amini ◽

Nastaran Pedram ◽

...

Keyword(s):

Stem Cells ◽

Mammary Gland ◽

Lymph Node ◽

Cancer Stem Cells ◽

Vasculogenic Mimicry ◽

Lymph Node Status ◽

Mesenchymal Transition ◽

Node Status ◽

Canine Mammary Gland ◽

Histopathologic Features

Abstract The purpose of the present work was the evaluation of the prognostic potential of histopathologic features, cancer stem cells (CSCs), and epthelial-mesenchymal transition (EMT) in relation to lymph node status and lymphovascular invasion (LVI) in canine mammary gland carcinomas (CMGCs). CSCs are proposed as the main cause of tumorigenesis, therapy failure, and recurrence which form a small fraction of tumor bulk. We evaluated presence of micropapillary growth pattern (MGP), infiltration into surrounding tissues (IST), and vasculogenic mimicry (VM) in H&E stained slides of 26 paraffin-embedded tumor samples. Lymph nodes of all cases were assessed. Additionally, they were examined immunohistochemically in terms of vimentin expression as an indicator of EMT which is a well-known mechanism for metastasis, and CD44, CD24, and ALDH1 for CSCs detection. Data analyses showed significant relationships between MGP and CSCs (P = 0.037), VM and CSCs (P = 0.013), lymph node status and CSCs (P = 0.0001), lymph node status and EMT (P = 0.003), IST and LVI (P = 0.05), VM and LVI (P = 0.01), VM and lymph node status (P = 0.007), and LVI and lymph node status (P = 0.04). Results indicated the prognostic value of MGP, VM, and CSCs with respect to confirmed prognostic markers, including LVI and lymph node involvement, in CMGCs.

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Aberrant Expression of Markers of Cancer Stem Cells in Gastric Adenocarcinoma and their Relationship to Vasculogenic Mimicry

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2015.16.10.4177 ◽

2015 ◽

Vol 16 (10) ◽

pp. 4177-4183 ◽

Cited By ~ 7

Author(s):

Lei Zhou ◽

Lan Yu ◽

Zhen-Zhong Feng ◽

Xiao-Meng Gong ◽

Ze-Nong Cheng ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Gastric Adenocarcinoma ◽

Vasculogenic Mimicry ◽

Aberrant Expression

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A new perspective of vasculogenic mimicry: EMT and cancer stem cells (Review)

Oncology Letters ◽

10.3892/ol.2013.1555 ◽

2013 ◽

Vol 6 (5) ◽

pp. 1174-1180 ◽

Cited By ~ 80

Author(s):

YUN-LONG FAN ◽

MIN ZHENG ◽

YA-LING TANG ◽

XIN-HUA LIANG

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Vasculogenic Mimicry ◽

New Perspective

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Transdifferentiation of cancer stem cells into endothelial cells

Open Life Sciences ◽

10.2478/s11535-011-0055-3 ◽

2011 ◽

Vol 6 (5) ◽

pp. 850-852

Author(s):

Caterina Porta

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Poor Prognosis ◽

Vasculogenic Mimicry ◽

Three Dimensional ◽

Stem Cell Population ◽

Vascular Networks ◽

Endothelial Phenotype ◽

Aggressive Tumors ◽

Unique Ability

AbstractVasculogenic mimicry was first described as the unique ability of aggressive melanoma cells to express an endothelial phenotype and to form vessel-like networks in three dimensional cultures, “mimicking” the pattern of embryonic vascular networks and recapitulating the patterned networks seen in patients with aggressive tumors correlated with poor prognosis. Recent work shows the occurrence of alternative vasculogenic patterns is due to the presence of stem cell population (cancer stem cells, CSC) at least in melanoma and glioblastoma. In the present review the new perspectives to target vasculogenic mimicry for an anti-vascular treatment strategy and the possible use of AQP1 as target, are discussed. Interest in AQP1 as a target arises from the pivotal role it plays in the organisation of vascular network affecting the cytoskeleton.

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