Inflammatory Angiogenesis and the Tumor Microenvironment as Targets for Cancer Therapy and Prevention

Abstract

In addition to aberrant transformed cells, tumors are tissues that contain host components, including stromal cells, vascular cells (ECs) and their precursors, and immune cells. All these constituents interact with each other at the cellular and molecular levels, resulting in the production of an intricate and heterogeneous complex of cells and matrix defined as the tumor microenvironment. Several pathways involved in these interactions have been investigated both in pathological and physiological scenarios, and diverse molecules are currently targets of chemotherapeutic and preventive drugs. Many phytochemicals and their derivatives show the ability to inhibit tumor progression, angiogenesis, and metastasis, exerting effects on the tumor microenvironment. In this review, we will outline the principal players and mechanisms involved in the tumor microenvironment network and we will discuss some interesting compounds aimed at interrupting these interactions and blocking tumor insurgence and progression. The considerations provided will be crucial for the design of new preventive approaches to the reduction in cancer risk that need to be applied to large populations composed of apparently healthy individuals.

Bone marrow derived myeloid cells orchestrate antiangiogenic resistance in glioblastoma through coordinated molecular networks

“…vatalanib, cediranib, sunitinib, etc. have been used against VEGF-VEGFR pathway to control abnormal angiogenesis in clinical trials [14, 21, 50, 62-64]. Regrettably, benefits of AATs are at best transitory, and this period of clinical benefit is followed by restoration of tumor growth [49].…”

Nutrigenomics of extra‐virgin olive oil: A review

“…This is a physiologic process regulated through the fine balance between stimulatory factors, such as Vascular Endothelial Growth Factor (VEGF), basic Fibroblast Growth Factor (bFGF), Placental Growth Factor (PlGF), inhibitory factors as Tissue Inhibitor of MetalloProteinase (TIMP), Angiopoietin‐2 (Ang‐2), Interferon‐α (IFN‐α), Thrombospondin family of genes (TSP) and other molecular players with accessory pro‐angiogenic properties, such as endothelial Nitric Oxide Synthase (eNOS) and COX‐2. This process could shift to a pathological condition when feedback mechanisms are deficient or completely lost, a condition promoted by the tumor microenvironment, that is the cellular environment surrounding the tumor, including blood vessels, immune cells, fibroblasts and signaling molecules . Tumor and microenvironment are closely related and interact constantly by the release of extracellular signals that promote tumor angiogenesis and pro‐tumoral stimuli.…”

Validation of the effects of TGF-β1 on tumor recurrence and prognosis through tumor retrieval and cell mechanical properties

“…We also noted that CD31-expressing endothelial cells occupied the sites of angiogenesis (Figure  4A and B). Tumor angiogenesis contributes to tumor cell proliferation and metastasis by supplying oxygen and nutrients and removing cellular wastes [49,50]. …”