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

  • Antonino Bruno
  • Arianna Pagani
  • Elena Magnani
  • Teresa Rossi
  • Douglas M. Noonan
  • Anna Rita Cantelmo
  • Adriana Albini
Conference paper
Part of the Cancer Treatment and Research book series (CTAR, volume 159)

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.

Keywords

Tumour microenvironment Angiogenesis Inflammation Anti-angiogenic therapy Chemoprevention 

Abbreviation

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

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Antonino Bruno
    • 1
  • Arianna Pagani
    • 1
    • 3
  • Elena Magnani
    • 4
  • Teresa Rossi
    • 2
  • Douglas M. Noonan
    • 3
    • 4
  • Anna Rita Cantelmo
    • 4
  • Adriana Albini
    • 2
  1. 1.Polo Scientifico e TecnologicoMultiMedica OnlusMilanoItaly
  2. 2.Research InfrastructureIRCCS Arcispedale Santa Maria NuovaReggio EmiliaItaly
  3. 3.Department of Biotechnologies and Life SciencesUniversity of InsubriaVareseItaly
  4. 4.Polo Scientifico e TecnologicoMultiMedica IRCCSMilanoItaly

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