Differences of Angiogenesis Factors in Tumor and Diabetes Mellitus

Figures & data

Figure 1 Interactions between angiogenic factors in diabetes mellitus and cancer. Hypoxia and hyperglycemia are the main characteristics of the microenvironment of tumor and diabetes mellitus. Hypoxia mainly promotes angiogenic factors, while hyperglycemia mainly inhibits them. VEGF, HIF-1, SDF-1, Ang-2, FGF and so on are the main factors affecting angiogenesis. EPCs, Pericytes, TAMS, CAFs, etc. These are the main cells involved in angiogenesis. These factors and cells are closely related to each other. It is the presence of these connections and pathways that account for the huge differences in angiogenesis between diabetes mellitus and tumors.

Table 1 New Advances of Angiogenesis Factors in Tumor and Diabetes

Factors Influencing Angiogenesis	Tumor	Diabetes Mellitus
VEGF^1	high expression, promotes angiogenesis	low expression, promotes angiogenesis
HIF-1^2	high expression, promotes angiogenesis	low expression, promotes angiogenesis
NO^3	high expression, promotes/inhibits angiogenesis	low expression, promotes angiogenesis
SDF-1^4/ CXCR4^5	high expression, promotes angiogenesis	low expression, promotes angiogenesis
COX-2^6/mPGES-1^7/PGE2^8	high expression, promotes angiogenesis	low expression, promotes angiogenesis
MMP^9-1	high expression, promotes angiogenesis	low expression, promotes angiogenesis
MMP-2	high expression, promotes angiogenesis	low expression, promotes angiogenesis
MMP-9	high expression, promotes /inhibits angiogenesis	high/low expression, promotes /inhibits angiogenesis
ROS^10	high expression, promotes angiogenesis	high expression, inhibits angiogenesis
FGF^11	high expression, promotes angiogenesis	high expression/normal, promotes angiogenesis
PAI-1^12	high expression, promotes /inhibits angiogenesis	high expression, inhibits angiogenesis
TNF-α^13	high expression, promotes angiogenesis	high expression, promotes angiogenesis
TGF^14-β	high expression, promotes angiogenesis	high/low expression, promotes angiogenesis
Exosomes	production increased, promotes angiogenesis	production increased, promotes /inhibits angiogenesis
PDGF^15	high expression, promotes /inhibits angiogenesis	high expression, promotes angiogenesis
Wnt^16/β-catenin	high expression, promotes angiogenesis	high expression, promotes angiogenesis
Ang-2^17	high expression, promotes angiogenesis	high expression, promotes angiogenesis
IGF1^18	high expression, promotes angiogenesis	low expression, promotes angiogenesis
Leptin	high expression, promotes angiogenesis	high expression, promotes angiogenesis
IGAM-1^19	high expression, promotes angiogenesis	high expression, promotes angiogenesis
Nrp1^20	high expression, promotes angiogenesis	low expression, promotes angiogenesis
Semaphorins	high expression, promotes/inhibits angiogenesis	high expression, promotes angiogenesis
miRNAs^21	high/low expression, promotes /inhibits angiogenesis	high/low expression, promotes /inhibits angiogenesis
AGEs^22		high expression, promotes/inhibits angiogenesis
gFGF^23		high expression, inhibits angiogenesis
PEDF^24	low expression, inhibits angiogenesis	high expression, inhibits angiogenesis
SHP-1^25	high/low expression, inhibits angiogenesis	high expression, inhibits angiogenesis
Endostatin	low expression, inhibits angiogenesis	high expression, inhibits angiogenesis
Angiostatin	low expression, inhibits angiogenesis	high expression, inhibits angiogenesis
Pericytes	sparse, promotes angiogenesis	lost, stabilize new blood vessels
EPCs^26		decline in activity/number, promotes angiogenesis
TAMs^27	activated, promotes angiogenesis
CAFs^28	activated, promotes angiogenesis
MSCs^29	activated, promotes angiogenesis	inhibited, promotes angiogenesis
Overall effect	Angiogenesis is enhanced	Angiogenesis is reduced

Notes: ¹ vascular endothelial growth factor; ² hypoxia inducible factor-1; ³ nitric oxide; ⁴ stromal cell-derived factor-1; ⁵ the receptor CXC chemokine receptor type 4; ⁶ cyclooxygenase-2; ⁷ microsomal prostaglandin E synthase-1; ⁸ prostaglandin E2; ⁹ matrix metalloproteinases; ¹⁰ reactive oxygen species; ¹¹ fibroblast growth factor; ¹² plasminogen activator inhibitor-1; ¹³ tumor necrosis factor-alpha; ¹⁴ transforming growth factor; ¹⁵ platelet-derived growth factor; ¹⁶ Wingless and Int-related protein; ¹⁷ angiopoietins 2; ¹⁸ Insulin-like growth factor 1; ¹⁹ intercellular adhesion molecule - 1; ²⁰ neuropilin 1; ²¹microRNA; ²²advanced glycation end products; ²³ basic fibroblast growth factor; ²⁴ platelet derived growth factor; ²⁵ SRc homology-2-domain-containing phosphatase-1; ²⁶ Endothelial precursor cells; ²⁷ tumor-associated macrophages; ²⁸ cancer associated fibroblasts; ²⁹Mesenchymal stem cells.