Abstract
Analysis of bioactive substances produced by cancer cells is one approach to understanding the biological features of human cancer. One of these bioactive substances is endothelin (ET)-1, a peptide with potent vasoconstrictive activity produced by vascular endothelial cells. We have previously reported the production of ET-1 by several types of human cancer, especially pancreatic cancer cells. To elucidate whether these cancer cells might share biological characteristics with vascular endothelial cells, we investigated the production of three ET isoforms in pancreatic cancer cells, using a specific radioimmunoassay. Further, we also investigated whether these cells produce thrombomodulin (TM), another product of endothelial cells functioning as a modulator of procoagulant activity. ET-1 was detected in 11 of 12 pancreatic cancer cell lines (92%) while ET-2 and ET-3 were detectable in only one cell line. Gel filtration analysis confirmed the presence of ET-1. Moreover, TM was detected in the cell lysates of 11 of the 12 cell lines (92%) and it was released into the culture medium in the majority (58%) of these cell lines. TM mRNA was also detected in these cells. In addition, TM was demonstrated immunocytochemically along the cell surface. These results suggest that pancreatic cancer cells share two characteristics with endothelial cells: the production of ET-1 and TM.
Highlights
Synthetic human ET-1, ET-2 and ET-3 were purchased from the Peptide Institute (Osaka, Japan); porcine thyroglobulin
When the cross-reactivity of ET-2 was taken to be 100%, the cross-reactivities of ET-1, big ET-1 and ET-3 were 0.003%, 0.008% and less than 0.002% respectively
When the cross-reactivity of ET-3 was taken to be 100%, the cross-reactivities of ET-1, big ET-1 and ET-2 were less than 0.005%
Summary
Synthetic human ET-1, ET-2 and ET-3 were purchased from the Peptide Institute (Osaka, Japan); porcine thyroglobulin. Sixteen human malignant cell lines were examined. These were 12 pancreatic cancer cell lines (ASPC-1, BxPC-3, FA-6, MIAPaCa-2, PANC-1, PSN-1, KP1N, KP2, KP3, H48N, CAPAN-1 and CAPAN-2), a gastric cancer cell line (MKN28), a lung cancer cell line (A-549), a melanoma cell line (SEKI) and an acute promyelocytic leukaemia cell line (HL-60). PSN-1 and SEKI were established at the National Cancer Center Research Institute (Tokyo, Japan) (Shimoyama, 1975; Yamada et al, 1986). Nagata (National Defense Medical College, Saitama, Japan) (Nagata et al, 1989).
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