Pro-angiogenic activity and vasculogenic mimicry in the tumor microenvironment by leptin in cancer

Hematogenous and lymphogenous cancer metastases are significantly impacted by tumor neovascularization, which predominantly consists of blood vessel-relevant angiogenesis, vasculogenesis, vasculogenic mimicry, and lymphatic vessel-related lymphangiogenesis. Among the endothelial cells that make up the lining of tumor vasculature, a majority of them are tumor-derived endothelial cells (TECs), exhibiting cytogenetic abnormalities of aneuploid chromosomes. Aneuploid TECs are generated from “cancerization of stromal endothelial cells” and “endothelialization of carcinoma cells” in the hypoxic tumor microenvironment. Both processes crucially engage the hypoxia-triggered epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT). Compared to the cancerization process, endothelialization of cancer cells, which comprises the fusion of tumor cells with endothelial cells and transdifferentiation of cancer cells into TECs, is the dominant pathway. Tumor-derived endothelial cells, possessing the dual properties of cancerous malignancy and endothelial vascularization ability, are thus the endothelialized cancer cells. Circulating tumor-derived endothelial cells (CTECs) are TECs shed into the peripheral circulation. Aneuploid CD31+ CTECs, together with their counterpart CD31- circulating tumor cells (CTCs), constitute a unique pair of cellular circulating tumor biomarkers. This review discusses a proposed cascaded framework that focuses on the origins of TECs and CTECs in the hypoxic tumor microenvironment and their clinical implications for tumorigenesis, neovascularization, disease progression, and cancer metastasis. Aneuploid CTECs, harboring hybridized properties of malignancy, vascularization and motility, may serve as a unique target for developing a novel metastasis blockade cancer therapy.

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Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment

Journal of Oncology ◽

10.1155/2013/183602 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 27

Author(s):

Simona Berardi ◽

Roberto Ria ◽

Antonia Reale ◽

Annunziata De Luisi ◽

Ivana Catacchio ◽

...

Keyword(s):

Multiple Myeloma ◽

Drug Resistance ◽

Tumor Microenvironment ◽

Plasma Cell ◽

Plasma Cells ◽

Proteolytic Enzymes ◽

Vasculogenic Mimicry ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Growth And Survival

Tumor microenvironment is essential for multiple myeloma (MM) growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM) microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management.

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HIF-1α promoted vasculogenic mimicry formation in hepatocellular carcinoma through LOXL2 up-regulation in hypoxic tumor microenvironment

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-017-0533-1 ◽

2017 ◽

Vol 36 (1) ◽

Cited By ~ 46

Author(s):

Meili Wang ◽

Xiulan Zhao ◽

Dongwang Zhu ◽

Tieju Liu ◽

Xiaohui Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Vasculogenic Mimicry ◽

Hypoxic Tumor

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Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma

Cell & Bioscience ◽

10.1186/s13578-020-00488-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jie Zhang ◽

Chaoyu Gu ◽

Qianqian Song ◽

Mengqi Zhu ◽

Yuqing Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Microenvironment ◽

Immune Cells ◽

Vasculogenic Mimicry ◽

Cancer Associated Fibroblasts ◽

Biological Functions ◽

Ecm Remodeling ◽

Downstream Signaling ◽

Cellular Origin ◽

Suppressive Phenotype

Abstract The tumor microenvironment (TME) is a complex multicellular functional compartment that includes fibroblasts, myofibroblasts, endothelial cells, immune cells, and extracellular matrix (ECM) elements. The microenvironment provides an optimum condition for the initiation, growth, and dissemination of hepatocellular carcinoma (HCC). As one of the critical and abundant components in tumor microenvironment, cancer-associated fibroblasts (CAFs) have been implicated in the progression of HCC. Through secreting various growth factors and cytokines, CAFs contribute to the ECM remodeling, stem features, angiogenesis, immunosuppression, and vasculogenic mimicry (VM), which reinforce the initiation and development of HCC. In order to restrain the CAFs-initiated HCC progression, current strategies include targeting specific markers, engineering CAFs with tumor-suppressive phenotype, depleting CAFs’ precursors, and repressing the secretions or downstream signaling. In this review, we update the emerging understanding of CAFs in HCC, with particular emphasis on cellular origin, phenotypes, biological functions and targeted strategies. It provides insights into the targeting CAFs for HCC treatment.

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