Role of sperm-associated antigen 9, tumor associated macrophages and vascular endothelial growth factor on angiogenesis and tumor progression in non-small cell lung cancer patients

Tumor microenvironment is typically consists of stromal and chronic inflamatuar cells, growing vascular cells and host's inflamatuar cells. It is thought, this microenvironment plays an important role in cancer progression. There is a broad spectrum of leukocytes in tumor microenvironment and these leukocytes has bifasic effect on tumor progression; immune cells eliminates tumor cells and acts as anti-tumoral but also when stimulated by appropriate tumor cells, they cause tumor progression. Other well known components of tumor microenvironment are 'tumor associated macrophages (TAMs)' and these TAMs produce many mediators, one of them is chemocins which provide activation and progression of chronic inflammatuary process. Also it is shown that number of TAM is correlated with tumor cell apoptosis and CD8+ lymphocytes. The potential significance of TAMs at lung cancer patients is shown with correlation between high numbers of TAMs and poor prognosis. Tumors can't grow up more than 2-3 mm3 without neovascularisation. Tumors must be supported with new blood vessels and formation of vessels is a complex process including proliferation and migration of endothelial cells. Tumor cells express enzymes, growth factors and angiogenic substances for stimulating this neovacularisation cascade. The prototype of vascular growth factors is 'vascular endothelial growth factor (VEGF). VEGF is an angiogenic factor involved in endothelial cell proliferation and so tumor angiogenesis and progression. It up-regulates permeability of vessels and effects endothelial cell proliferation. Recent studies has showed correlation between poor prognosis in non-small cell lung cancer patients and VEGF overexpression. Sperm-associated antigen 9 is a member of cancer testis antigen (CTA) family which is expressed and causes strong immune response in many cancers. CTAs are proteins primarily expressed in normal testis tissue. These antigens may be expressed in other normal tissues at very low levels while high levels of expression at many cancerous tissues can be seen. At recent studies with non-small cell lung cancer patients, expression of SPAG9 protein at cancereus tissue is higher when compared with adjacent non-cancereus tissue and these patients with high SPAG9 expressoin had poor prognosis. Also down-regulation of SPAG9 results in reduced expression of VEGF so decreased vascularisation. In our study, with recent studies, we aimed to investigate association between SPAG9 protein expression and TAMs with VEGF and CD4/CD8 lymphocytes in non-small cell lung cancer. We selected 80 non-small cell lung cancer patients diagnosed and operated at Baskent University Hospital between 2011 January and 2016 May. Hemotoksilen&eosin sections were reviewed again, clinicopathologic parameters were analysed. Also SPAG9, VEGF, CD68, CD4 and CD8 antibodies were aplied with immunohistochemistry to all patients. We tried to analyze the effect of SPAG9 expression on tumor progression and VEGF, also activity of TAM and lymphocites at tumor microenvironment at NSCLC patients. It is known that SPAG9 expression promotes tumor progression, tumor cell invasion, migration and metastatic ability at NSCLC patients. In our study, high SPAG9 expression is correlated with lymphovascular invasion and TNM stage. Also patients with high SPAG9 expression showed higher VEGF expression. We also know that TAMs and lypmhocites at tumor microenvironment are associated with tumor progression. In a smilar manner, tumors with high number of TAMs are found to have advanced stage. In conclusion, we think SPAG9 and TAMs are correlated with poor prognosis, still we can say more stydies with higher number of patients are required.