PC-3 prostate carcinoma cells release signal substances that influence the migratory activity of cells in the tumor's microenvironment

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.

N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting

“…In PC-3, tunicamycin also effectively blocked N -glycosylation. However, in these cells the basal high expression of LCN2 was not further triggered by addition of IL-1β, most likely due to the fact PC-3 cells release large quantities of IL-1β, IL-1α (Voss et al, 2010 ), and IL-6 (Okamoto et al, 1997 ) leading to autocrine stimulation of LCN2 expression by these cytokines (Borkham-Kamphorst et al, 2011 ). Although IL-1β-stimulated A549 express only low quantities of LCN2, we were able to demonstrate that both, glycosylated and unglycosylated LCN2 variants, were targeted into exosomes (Figure 7 ).…”

Escaping from, moving towards, following a path, squeezing through: lots of opportunities for moving cells

“…In this special issue Voss and Entschladen review this aspect with a particular focus on the role of cathecolamine and stress mediators on tumoral cell motility [13]. …”

“…The nervous system also plays an important role in cell motility, for two reasons: the secretion of neurotransmitters which also act as motility factors and the contribution of an alternative escaping way to migrating cells, commonly called perineural invasion. In this special issue Voss and Entschladen review this aspect with a particular focus on the role of cathecolamine and stress mediators on tumoral cell motility [ 13 ].…”