Angiogenic Pathways

The expression of angiogenic factors by tumor cells varies between different tumor cell types and with time in any particular tumor or its subclones. In cross-sectional studies, malignant tumors of increasingly advanced stage 

As well as differing between tumors of different types, angiogenic factor expression may vary between individual tumor cells within a tumor. This heterogeneous production of factors between subclones of tumor cells within a primary tumor is reflected by variations in factor production between primary tumors and their metastases [52], Indeed, inconsistent relationships between matched individual tumors and their metastatic deposits in their levels of vascularity and endothelial cell proliferation may indicate that angiogenic factor production by the metastasizing clone differs from that in the primary tumor [53], 

It is difficult to determine from cross-sectional studies whether new induction of angiogenic factors leads sequentially to tumor progression, as implied 

Variations in the expression of angiogenic factors may modulate tumor vascularization and therefore oxygenation. This, in turn, may contribute to differing responsiveness to treatments between different tumor cell types. For example, increased radioresistance in pancreatic carcinoma cell lines was associated with an increased expression of angiopoietin (Ang)-2, which plays an important role in vascular maturation [56]. 

In addition to differences between tumors and their environment, the neo vascular phenotype itself may differ between tissues. A variety of vascular morphologies has been discussed above, and specific molecules expressed by the neovasculature may also vary. For example, binding of the antiangiogenic factor endostatin was found to almost all bladder tumor vessels, three quarters of the vessels in prostatic carcinomas, and only 11% of renal tumor vessels [63]. VEGFR3, which, in most tissues, is restricted to lymphatics, has been identified in the new blood vessels of inflamed synovium [26]. These and other characteristics of different neo vascular beds may contribute to heterogeneous responses to therapies that target the vasculature. 

---

Friedlander M, Brooks PC, Shaffer R et al (1995) Definition of two angiogenic pathways by distinct av integrins. Science 27 1500-1502... 

Different tissues may utilize various angiogenic pathways that are modulated by diverse host tissue responses. Furthermore, a single tissue may progress through a sequence of angiogenic pathways, for example, as acute injury progresses to chronic inflammation. The phenotype of the resulting neovasculature is critically dependent on the context in which it is formed. 

Several vasoactive peptides provide examples where one angiogenic pathway gives way to another, thereby maintaining angiogenesis. This plasticity of angiogenic pathways emphasizes the need to extend studies in normal tissues by undertaking research on pathological samples, since factors that are important in one may be redundant in the other. 

CBO-Pll, a specific inhibitor of vascular endothelial growth factor and other angiogenic pathways, was efficiently incorporated in multifunctional anti-VC AM-1 and anti-ICAM-1 polyurethane-urea nanoparticles." These systems showed a significant and selective blockade of the proliferation only in inflamed endothelial cells and no cytotoxic effect was observed in healthy cells. Moreover, in vivo studies in CDl mice demonstrated that these nanoparticles reach the target site after intravenous administration. 

Slevin, M. et al., Angiogenic oligosaccharides of hyaluronan induce protein tyrosine kinase activity in endothelial cells and activate a cytoplasmic signal transduction pathway resulting in proliferation,... 

---