1.
Endothelial Progenitors in the Tumor Microenvironment.
Testa, U, Pelosi, E, Castelli, G
Advances in experimental medicine and biology. 2020;:85-115
Abstract
Tumor vascularization refers to the formation of new blood vessels within a tumor and is considered one of the hallmarks of cancer. Tumor vessels supply the tumor with oxygen and nutrients, required to sustain tumor growth and progression, and provide a gateway for tumor metastasis through the blood or lymphatic vasculature. Blood vessels display an angiocrine capacity of supporting the survival and proliferation of tumor cells through the production of growth factors and cytokines. Although tumor vasculature plays an essential role in sustaining tumor growth, it represents at the same time an essential way to deliver drugs and immune cells to the tumor. However, tumor vasculature exhibits many morphological and functional abnormalities, thus resulting in the formation of hypoxic areas within tumors, believed to represent a mechanism to maintain tumor cells in an invasive state.Tumors are vascularized through a variety of modalities, mainly represented by angiogenesis, where VEGF and other members of the VEGF family play a key role. This has represented the basis for the development of anti-VEGF blocking agents and their use in cancer therapy: however, these agents failed to induce significant therapeutic effects.Much less is known about the cellular origin of vessel network in tumors. Various cell types may contribute to tumor vasculature in different tumors or in the same tumor, such as mature endothelial cells, endothelial progenitor cells (EPCs), or the same tumor cells through a process of transdifferentiation. Early studies have suggested a role for bone marrow-derived EPCs; these cells do not are true EPCs but myeloid progenitors differentiating into monocytic cells, exerting a proangiogenic effect through a paracrine mechanism. More recent studies have shown the existence of tissue-resident endothelial vascular progenitors (EVPs) present at the level of vessel endothelium and their possible involvement as cells of origin of tumor vasculature.
2.
How many cadherins do human endothelial cells express?
Colás-Algora, N, Millán, J
Cellular and molecular life sciences : CMLS. 2019;(7):1299-1317
Abstract
The vasculature is the paradigm of a compartment generated by parallel cellular barriers that aims to transport oxygen, nutrients and immune cells in complex organisms. Vascular barrier dysfunction leads to fatal acute and chronic inflammatory diseases. The endothelial barrier lines the inner side of vessels and is the main regulator of vascular permeability. Cadherins comprise a superfamily of 114 calcium-dependent adhesion proteins that contain conserved cadherin motifs and form cell-cell junctions in metazoans. In mature human endothelial cells, only VE (vascular endothelial)-cadherin and N (neural)-cadherin have been investigated in detail. Although both cadherins are essential for regulating endothelial permeability, no comprehensive expression studies to identify which other family members could play a relevant role in endothelial cells has so far been performed. Here, we have reviewed gene and protein expression databases to analyze cadherin expression in mature human endothelium and found that at least 24 cadherin superfamily members are significantly expressed. Based on data obtained from other cell types, organisms and experimental models, we discuss their potential functions, many of them unrelated to the formation of endothelial cell-cell junctions. The expression of this new set of endothelial cadherins highlights the important but still poorly defined roles of planar cell polarity, the Hippo pathway and mitochondria metabolism in human vascular homeostasis.
3.
Adipocytokine Involvement in Innate Immune Mechanisms.
Żelechowska, P, Kozłowska, E, Pastwińska, J, Agier, J, Brzezińska-Błaszczyk, E
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 2018;(12):527-538
Abstract
The innate immune response is defined as an immensely complex and sophisticated process aimed at defending the organism against any disturbance in the body homeostasis, including invading pathogens. It requires a close cooperation of a vast amount of different cell types, recognized as inflammatory migrating cells, as well as stationary cells that form tissues. Moreover, innate immune mechanisms require an efficient functioning of various humoral components that exert a significant impact on physiological and pathological processes. Apart from commonly mentioned humoral factors, this group also includes a family of proteins known as adipocytokines that may act as pro- or anti-inflammatory agents or act both ways. Leptin, predominantly characterized as a proinflammatory adipokine, plays a crucial role in endothelium remodeling and regulation, as well as in cell survival and production of numerous cytokines. Adiponectin, similar to leptin, acts on the endothelial cells and the phagocytic properties of immune cells; however, it exerts an anti-inflammatory impact. Resistin has a documented role in the control of angiogenesis and stimulation of proinflammatory mediator generation and release. Furthermore, there are adipokines, ie, visfatin and chemerin, whose participation in the inflammatory processes is ambiguous. This review focuses on the current knowledge on the extensive role of selected adipokines in innate immune response.