Crosstalk between cancer cells and endothelial cells: implications for tumor progression and intervention

Abstract

Communication between tumor cells and stromal cells is crucial to tumor development and progression. Fibroblasts and macrophages are the most common stromal cells in the tumor microenvironment. Endothelial cells are another type of stromal cell in the tumor microenvironment required for angiogenesis via interaction with tumor cells. Tumor angiogenesis provides not only oxygen and nutrients for tumor cells but also the necessary anchorage to facilitate tumor metastasis. The present review summarizes studies on the crosstalk between cancer cells and endothelial cells with a focus on implications for tumor progression. The following four categories are discussed in this review: (1) cell-cell communication in tumor microenvironment; (2) induction of metastasis by interaction between cancer cells and endothelial cells; (3) angiogenesis induced by tumor cells; (4) therapeutic strategies targeting adhesion and signaling molecules as well as chemokines. This review provides useful information highlighting the process of cancer aggressiveness affected by the crosstalk between cancer cells and endothelial cells, and suggests therapeutic strategies against tumor progression.

Putting VE-cadherin into JAIL for junction remodeling

“…The vascular endothelium is composed from ECs that are connected to each other via cell junctions; they form a highly dynamic and plastic interface between the blood stream and the interstitial tissue, controlling exchange of water and solutes. EC junctions also play a critical role in regeneration, vasculogenesis and angiogenesis, inflammation and tumor progression (for reviews, see Vestweber, 2012;Fromel and Fleming, 2015;Kazmi et al, 2015;Tesfamariam, 2016;Zou et al, 2016;Filipowska et al, 2017;Godo and Shimokawa, 2017;Szymborska and Gerhardt, 2017;Choi and Moon, 2018;Hida et al, 2018). ECs and EC junctions undergo a specific and different differentiation program in organs and vascular segments (Simionescu et al, 1975(Simionescu et al, , 1976a(Simionescu et al, ,b, 1983Corada et al, 1999;Dejana et al, 2008;Frye et al, 2015;Augustin and Koh, 2017); thus a heterogeneous regulation and dynamics can be assumed (Trepat and Fredberg, 2011).…”

Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers

“…Structure, Cells, and Signaling TME is a web of cancer-associated fibroblasts, immune cells, extracellular matrix, and vasculature ( Figure 1). It is hypothesized that the crosstalk between cancer cells and their surrounding environmental factors plays a pivotal role in tumor development [11]. Intriguingly, each component in TME may play invert roles in early or advanced tumors, which may bring more complicated challenges for cancer therapy.…”

“…Endothelial cells in TME have also been considered to interact with cancer cells [11]. Recently, the concept of "angiocrine factors" has emerged, which are released from tumor endothelial cells, such as adhesion molecules and chemokines, and vital for tumor progression and metastasis [29].…”

“…In glioma carcinoma, EVs secreting from cancer cells promote angiogenesis and metastasis through directly transferring RNA and proteins, such as EGFRvIII and TF/VIIa, into endothelial cells [32]. Studies investigate that the anticancer therapy targeting cytokine secretion of endothelial cells may be a new breakthrough for chemotherapeutic agents [11].…”

“…Meanwhile, stromal cell-derived EVs are capable of affecting the proliferation, drug resistance, and stem cell properties of cancer cells [8]. EVs also mediated the crosstalk between cancer cells and diverse TME cells such as adipocytes, fibroblasts, bone marrow cells, and immune cells [11]. Emerging evidence suggests that tumor cells secrete more EVs than normal cells.…”