Abstract
BackgroundTumor cells interact with the cells of the microenvironment not only by cell-cell-contacts but also by the release of signal substances. These substances are known to induce tumor vascularization, especially under hypoxic conditions, but are also supposed to provoke other processes such as tumor innervation and inflammatory conditions. Inflammation is mediated by two organ systems, the neuroendocrine system and the immune system. Therefore, we investigated the influence of substances released by PC-3 human prostate carcinoma cells on SH-SY5Y neuroblastoma cells as well as neutrophil granulocytes and cytotoxic T lymphocytes, especially with regard to their migratory activity.ResultsPC-3 cells express several cytokines and growth factors including vascular endothelial growth factors, fibroblast growth factors, interleukins and neurotrophic factors. SH-SY5Y cells are impaired in their migratory activity by PC-3 cell culture supernatant, but orientate chemotactically towards the source. Neutrophil granulocytes increase their locomotory activity only in response to cell culture supernantant of hypoxic but not of normoxic PC-3 cells. In contrast, cytotoxic T lymphocytes do not change their migratory activity in response to either culture supernatant, but increase their cytotoxicity, whereas supernatant of normoxic PC-3 cells leads to a stronger increase than that of hypoxic PC-3 cells.ConclusionsPC-3 cells release several signal substances that influence the behavior of the cells in the tumor's microenvironment, whereas no clear pattern towards proinflammatory or immunosuppressive conditions can be seen.
Highlights
Today's understanding of the biology of tumors increasingly shows a crucial role of the microenvironment in the tumors' growth and the course of the cancer disease
We have reported previously that hypoxic conditions lead to a change of the released substances' profile of PC-3 cells towards more inflammatory conditions similar to SH-SY5Y cells, e.g. by an increase of the release of interleukin-1 [17]
Neutrophil granulocytes and macrophages can make up to 50 percent of the total tumor mass in breast carcinoma [18], and neutrophil granulocytes are supposed to play a role in inflammationinduced angiogenesis [19,20]
Summary
Today's understanding of the biology of tumors increasingly shows a crucial role of the microenvironment in the tumors' growth and the course of the cancer disease. This environmental interactions concern the development of new blood vessels in tumors (called neoangiogenesis), which was one of the first tumor-stroma interactions described in 1971 by Judah Folkman and colleagues [1], as well as the development of new lymph vessels (lymphangiogenesis) [2], and the innervation of tumors, which we have termed neoneurogenesis [3,4]. We investigated the influence of substances released by PC-3 human prostate carcinoma cells on SH-SY5Y neuroblastoma cells as well as neutrophil granulocytes and cytotoxic T lymphocytes, especially with regard to their migratory activity
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