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.
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Abbreviations
- IGF1-R:
-
Insulin-like growth factor 1-receptor
- IκB:
-
Inhibitor kinase B
- IKK:
-
Inhibitor kinase kinase
- IL-13:
-
Interleukin-13
- IL-4:
-
Interleukin-4
- IL-6:
-
Interleukin-6
- IL-12:
-
Interleukin-12
- IL1Rα:
-
Interleukin-1 receptor-alpha
- IL1β:
-
Interleukin-1 beta
- JAK:
-
Activating Janus kinase
- MAPK:
-
Mitogen-activated phospho kinase
- MDM2:
-
Murine double minute 2
- MDM4:
-
Mouse double minute 4
- MDSC:
-
myeloid-derived suppressor cell
- MMP-1:
-
Matrix metallo protease-1
- MMP-2:
-
Matrix metallo protease-2
- MMP-7:
-
Matrix metallo protease-7
- MMP-9:
-
Matrix metallo protease-9
- mTOR:
-
Mammalian target of rapamycin
- N1:
-
N1-polarized neutrophils
- N2:
-
N2-polarized neutrophils
- NAC:
-
N-acetylcysteine
- NF-κB:
-
Nuclear factor-kappa B
- NSAIDs:
-
Non-steroidal anti-inflammatory drugs
- NSCLC:
-
Non-small cell lung cancer
- PDGF:
-
Platelet-derived growth factor
- PDGFR-β:
-
Platelet-derived growth factor receptor-beta
- PDGFR:
-
Platelet-derived growth factor receptor
- PI3K:
-
Phosphoinositide 3-kinase
- PIG3:
-
p53-inducible gene 3
- PlGF:
-
Placental growth factor
- PMNs:
-
Polymorphonuclear neutrophils
- Raf:
-
Root abundant factor
- RARs:
-
Retinoid acid receptors
- RARβ:
-
Retinoid acid receptor-beta
- RCC:
-
Renal cell carcinoma
- RelA:
-
NFkB subunit-A
- RelB:
-
v-rel reticuloendotheliosis viral oncogene homolog B
- RET:
-
Rearranged during transfection
- RHD:
-
Rel homology domain
- RITA:
-
Reactivation of p53 and induction of tumor cell apoptosis
- ROS:
-
Reactive oxygen species
- RTK:
-
Receptor tyrosine kinase
- STAT:
-
Signal transducer and activator of transcription
- STAT3:
-
Signal transducer and activator of transcription 3
- SV40:
-
Simian virus 40
- TAM:
-
Tumor-associated macrophage
- TEM:
-
Tie2-expressing macrophage
- TGFα:
-
Transforming growth factor-alpha
- TGFβ:
-
Transforming growth factor-beta
- Th:
-
T helper
- Th2:
-
T helper type-2 polarization
- TKIs:
-
Tyrosine kinase inhibitors
- TNF:
-
Tumor necrosis factor
- TNFα:
-
Tumor necrosis factor-alpha
- TP53TG1:
-
TP53 target 1
- TSP-1:
-
Thrombospondin-1
- VEGF-A:
-
Vascular endothelial growth factor A isoform
- VEGF:
-
Vascular endothelial growth factor
- VEGFR:
-
Vascular endothelial growth factor receptor
- vSMC:
-
Vascular smooth muscle cell
- WIP1:
-
Wound-induced protein 1
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Acknowledgments
These studies were supported by grants from the AIRC (Associazione Italiana per la Ricerca sul Cancro), the Ministero della Salute, the and ISS (Istituto Superiore della Sanità). AB is a FIRC (Fondazione Italiana per la Ricerca sul Cancro) fellow. AP is the recipient of the “Caterina Forni” AIRC fellowship. We thank Dr Paola Corradino (Multimedica IRCCS) for data management.
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Bruno, A. et al. (2014). Inflammatory Angiogenesis and the Tumor Microenvironment as Targets for Cancer Therapy and Prevention. In: Zappia, V., Panico, S., Russo, G., Budillon, A., Della Ragione, F. (eds) Advances in Nutrition and Cancer. Cancer Treatment and Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38007-5_23
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