Small cell lung cancer: circulating tumor cell lines and expression of mediators of angiogenesis and coagulation

Abstract

Introduction: Coagulation is frequently activated in cancer patients and has been correlated with an unfavorable prognosis. To evaluate whether a release of tissue factor (TF) of circulating tumor cells (CTCs) is involved in the dissemination of small cell lung cancer (SCLC) we studied the expression of relevant proteins in a panel of permanent SCLC and SCLC CTC cell lines (BHGc7, BHGc10, BHGc16, BHGc26 and UHGc5) that have been established at our institution. Material and Methods Five CTC and SCLC lines were analyzed using Western blot arrays covering 55 angiogenetic mediators. Furthermore, the influence of topotecan and epirubicin as well as hypoxia-like conditions on the expression of these mediators and cells was investigated. Results The results demonstrate that the SCLC lines express no significant amounts of the TF but thrombospondin-1 (TSP-1), uPAR, VEGF and angiopoietin-2 in two cases. The major difference between the SCLC and SCLC CTC cell lines found was the loss of the expression of angiogenin in the blood-derived CTC lines. Topotecan and epirubicin decreased expression of VEGF, whereas hypoxia-like conditions upregulated VEGF. Conclusions Active TF seems not to be expressed in SCLC and SCLC CTC cell lines in significant levels and, thus, CTC-derived TF seems dispensable for dissemination. Nevertheless, all CTC lines form large spheroids, termed tumorospheres, which may become trapped in clots of the microvasculature and extravasate in this supportive microenvironment. The contribution of clotting to protection and dissemination of CTCs in SCLC seems to be different from other solid tumors such as breast cancer.