In our study, pre operative levels of this angiogenic factor reference 2 were found significantly higher in the breast cancer group compared to the control group. Postoperatively, a transient in crease in circulating levels of VEGFA was documented for nearly all patients who underwent surgery for breast cancer 3 days after surgery which waned back 4 days later. FGF2 is another major proangiogenic cytokine. We found a trend towards increased levels in almost all patients, which has also been shown by others. Finally, IL8 increased only marginally Inhibitors,Modulators,Libraries after surgery on day 3 but settled down to values near the detection limit 1 week postsurgery. We also analyzed perioperative kinetics of circulating transcripts of angiogenesis related genes to profile Inhibitors,Modulators,Libraries gene expression patterns.
We first compared the results from the Inhibitors,Modulators,Libraries samples that were obtained preoperatively in both the control group and the cancer group. We found upregulation of a significant number of angiogenesis specific genes in breast cancer patients compared with controls sphingosine kinase 1, epidermal growth factor, vascular endothelial growth fac tor C, neuropilin 1, fibroblast growth factor, laminin alpha 5, collagen type IV alpha 3, IL8, ephrin B2, EFNA3, tyrosine endothelial kinase, integrin beta 3, V akt murine thymoma viral oncogene homolog 1, thrombospondin 1, chemokine ligand 11 and TIMP metallopeptidase inhibitor 3. This finding can be explained Inhibitors,Modulators,Libraries by the fact that, even at early stages of disease, the process of angiogenesis has already prompted upregulation of certain proangiogenic factors.
Some of the identified factors have an established role in the process of angiogenesis. EGF is overexpressed in triple negative breast cancer and has a synergic role to the induction of angiogenesis by VEGF. VEGFC binds to its receptor VEGFR3 and promotes lymphatic hyperplasia and lymphangiogenesis. FGF1 has also been shown to possess proangiogenic Inhibitors,Modulators,Libraries properties and IL8 is another established proangiogenic cytokine. However, the greatest amplification of genes was seen with SPHK1, EGF and VEGFC. SPHK1 is one of two generating enzymes of sphingosine 1 phosphate, which is an active sphingolipid metabolite. During the last decade, several studies have revealed the emerging role of S1P as a key molecule in human cancer development, angio genesis and lymphangiogenesis. Overexpression of SPHK1 in tumors is now believed to be the result of hypoxia and HIF1 induction.
Moreover, SPHK1 has been shown to have a prognostic significance in breast cancer. On the other hand, CXCL10, which is a member of the CXC chemokine family with potent antiangiogenic properties, was found to be downregulated in breast cancer patients. We also sought to determine the effect of surgery upon the process of angiogenesis by comparing considering any pos sible alterations in specific gene expression between the two groups of patients on postoperative day 3.