Overview of angiogenesis and oxidative stress in cancer

Table 1 Proliferation, migration, and differentiation by several factors/inductors implicated in angiogenesis

Inductors	Proliferation	Migration	Differentiation
Heparin-binding peptide growth factors
VEGF	Yes	Yes	Yes
PlGF	Weak	Yes	Unknown
FGF-1, FGF-2	Yes	Yes	Yes
PTN	Yes	Unknown	Yes
HIV-tat protein	Weak	Weak	Yes
PDGF	Yes	Yes	Yes
HGF/SF	Yes	Yes	Yes
Peptide growth factors that do not bind heparin
TGF-α	Yes	Yes	Yes
TGF-β	Inhibition	No	Yes
EGF	Yes	Yes	Yes
IGF-I	Yes	Yes	Yes
Inflammatory mediators
TNF-α	Inhibition	No	Yes
IL-8	Yes	Yes	Unknown
IL-3	Yes	Yes	Yes
Prostaglandins E1, E2	No	No	Yes
Enzymes
PD-ECGF/TP	No	Yes	Unknown
COX-2	No	Yes	Yes
Angiogenin	No	Yes	Yes
Hormones
Estrogen	Yes	Yes	Yes
Proliferin	Unknown	Yes	Unknown
Oligosaccharides
Hyaluronan oligosaccharides	Yes	Yes	Yes
Gangliosides	Unknown	Unknown	Unknown
Hematopoietic factors
Erythropoietin	Yes	Unknown	Yes
G-CSF	Yes	Yes	Unknown
GM-CSF	Yes	Yes	Unknown
Cell adhesion molecules
VCAM-1	No	Yes	Unknown
E-selectins	No	Yes	Yes
Integrins	No	Yes	Yes
Semaphorins (Sema3 e 4D)	No	Yes	Yes
Other
Nitric oxide	Yes	Unknow	Unknow
Angiopoietin-1	No	Yes	Yes

COX-2: Cyclooxygenase 2; EGF: Epidermal growth factor; FGF: Fibroblast growth factor; G-CSF: Granulocyte colony stimulating factor; GM-CSF: Granulocyte macrophage colony stimulating factor; HGF/SF: Hepatocyte growth factor/scatter factor; IGF: Insulin-like growth factor; IL: Interleukin; PD-ECGF/TP: Platelet-derived endothelial cell growth factor/thymidine phosphorylase; PlGF: Placental growth factor; PDGF: Platelet-derived growth factor; PTN, Pleiotrophin; TGF: Transforming growth factor; TNF: Tumor necrosis factor; VEGF: Vascular endothelial growth factor; VCAM: Vascular cell adhesion molecule.

Table 2 Molecular target of oxidative stress to promote tumor progression

Molecular target of ROS	Protein or gene	Function and mechanism	Tumor type
ERK1/ERK2	Protein	Promotion of cell proliferation and angiogenesis	Ovarian, colon, breast, and lung cancer
Nrf2	Protein	Regulation of oxidative stress by modulating the production of antioxidant enzymes	NSCLC and esophageal cancer
Ref1 /APE1	Protein	Reduction of ROS generation	Breast cancer
PTEN	Protein	Involvement in senescence; Association with high levels of Akt and ROS	Lung, liver, and breast cancer
Ras	Protein	Increases mitochondrial mass and ROS levels, causing DNA damage; Regulation of Nox4-p22phox system	30% of human cancer
mTOR	Protein	Promotion of cell proliferation and metabolism that contributes to tumor initiation and progression; Regulation of autophagy and apoptosis	More than 70% of cancers (breast, lung, colorectal, prostate, head and neck, gynecologic, urinary bladder, renal cancer gastric carcinoma, glioblastoma, lymphoma, and medulloblastoma)
P38	Protein	Regulation of cell proliferation, cell differentiation, cell death, cell migration, and invasion.	Prostate, breast, bladder, live, and lung cancer, transformed follicular lymphoma and leukemia
BRCA	Gene	Regulation of antioxidant response; Controlling the Nrf2 and NFκB activity	40%-50% of hereditary breast cancers
hTERT	Protein	Reduces oxidative stress intracellularly and extracellularly; Regulation of apoptosis	Gastric cancer, lung cancer, cervical and head cancer, glioblastoma, breast cancer, and ovarian cancer
Angiopoietin	Protein	Involvement in angiogenesis, lymphangiogenesis, and metastasis; Induction of hypoxia and cytokines	NSCLC

Akt: Protein kinase B; BRCA: Breast cancer gene; ERK1/2: Extracellular kinase 1/2; hTERT: Human telomerase reverse transcriptase; NRF2: Nuclear factor erythroid 2-related factor 2; NSCLC: Non-small cell lung carcinoma; PTEN: Phosphatase and homolog of tensin; mTOR: Mammalian target of rapamycin; Ref/APE1: Redox factor/Apurinic/apyrimidinic endonuclease 1; ROS: Reactive oxygen species.