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

<p>Abstract</p> <p>Background</p> <p>Tumor 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.</p> <p>Results</p> <p>PC-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.</p> <p>Conclusions</p> <p>PC-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.</p

Signal Transduction in the Footsteps of Goethe and Schiller

The historical town of Weimar in Thuringia, the "green heart of Germany" was the sphere of Goethe and Schiller, the two most famous representatives of German literature's classic era. Not yet entirely as influential as those two cultural icons, the Signal Transduction Society (STS) has nevertheless in the last decade established within the walls of Weimar an annual interdisciplinary Meeting on "Signal Transduction – Receptors, Mediators and Genes", which is well recognized as a most attractive opportunity to exchange results and ideas in the field

Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology

The 13th meeting of the Signal Transduction Society was held in Weimar, from October 28 to 30, 2009. Special focus of the 2009 conference was "Aging and Senescence", which was co-organized by the SFB 728 "Environmentally-Induced Aging Processes" of the University of Düsseldorf and the study group 'Signal Transduction' of the German Society for Cell Biology (DGZ). In addition, several other areas of signal transduction research were covered and supported by different consortia associated with the Signal Transduction Society including the long-term associated study groups of the German Society for Immunology and the Society for Biochemistry and Molecular Biology, and for instance the SFB/Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" located in Würzburg, Mainz and Berlin. The different research areas that were introduced by outstanding keynote speakers attracted more than 250 scientists, showing the timeliness and relevance of the interdisciplinary concept and exchange of knowledge during the three days of the scientific program. This report gives an overview of the presentations of the conference

Tumor interactions with soluble factors and the nervous system

In the genomic era of cancer research, the development of metastases has been attributed to mutations in the tumor that enable the cells to migrate. However, gene analyses revealed that primary tumors and metastases were in some cases genetically identical and the question was raised whether metastasis formation might be an inherent feature of certain tumor cells. In contradiction to this view, the last decade of cancer research has brought to light, that tumor cell migration, similar to leukocyte and fibroblast migration, is a highly regulated process. The nervous system plays an important role in this regulation, at least in two respects: firstly, neurotransmitters are known to regulate the migratory activity of tumor cells, and secondly, nerve fibers are used as routes for perineural invasion. We also summarize here the current knowledge on the innervation of tumors. Such a process might establish a neuro-neoplastic synapse, with the close interaction of tumor cells and nerve cells supporting metastasis formation

Extravasation of leukocytes in comparison to tumor cells

The multi-step process of the emigration of cells from the blood stream through the vascular endothelium into the tissue has been termed extravasation. The extravasation of leukocytes is fairly well characterized down to the molecular level, and has been reviewed in several aspects. Comparatively little is known about the extravasation of tumor cells, which is part of the hematogenic metastasis formation. Although the steps of the process are basically the same in leukocytes and tumor cells, i.e. rolling, adhesion, transmigration (diapedesis), the molecules that are involved are different. A further important difference is that leukocyte interaction with the endothelium changes the endothelial integrity only temporarily, whereas tumor cell interaction leads to an irreversible damage of the endothelial architecture. Moreover, tumor cells utilize leukocytes for their extravasation as linkers to the endothelium. Thus, metastasis formation is indirectly susceptible to localization signals that are literally specific for the immune system. We herein compare the extravasation of leukocytes and tumor cells with regard to the involved receptors and the localization signals that direct the cells to certain organs and sites of the body

Luminal and basal-like breast cancer cells show increased migration induced by hypoxia, mediated by an autocrine mechanism

<p>Abstract</p> <p>Background</p> <p>Some breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell migration was assessed in selected luminal, post-EMT and basal-like breast carcinoma cell lines.</p> <p>Methods</p> <p>Migration was assessed in luminal (MCF-7), post-EMT (MDA-MB-231, MDA-MB-435S), and basal-like (MDA-MB-468) human breast carcinoma cell lines under normal and oxygen-deprived conditions, using a collagen-based assay. Cell proliferation was determined, secreted cytokine and chemokine levels were measured using flow-cytometry and a bead-based immunoassay, and the hypoxic genes HIF-1α and CA IX were assessed using PCR. The functional effect of tumor-cell conditioned medium on the migration of neutrophil granulocytes (NG) was tested.</p> <p>Results</p> <p>Hypoxia caused increased migratory activity but not proliferation in all tumor cell lines, involving the release and autocrine action of soluble mediators. Conditioned medium (CM) from hypoxic cells induced migration in normoxic cells. Hypoxia changed the profile of released inflammatory mediators according to cell type. Interleukin-8 was produced only by post-EMT and basal-like cell lines, regardless of hypoxia. MCP-1 was produced by MDA-MB-435 and -468 cells, whereas IL-6 was present only in MDA-MB-231. IL-2, TNF-α, and NGF production was stimulated by hypoxia in MCF-7 cells. CM from normoxic and hypoxic MDA-MB-231 and MDA-MB-435S cells and hypoxic MCF-7 cells, but not MDA-MB-468, induced NG migration.</p> <p>Conclusions</p> <p>Hypoxia increases migration by the autocrine action of released signal substances in selected luminal and basal-like breast carcinoma cell lines which might explain why anti-angiogenic treatment can worsen clinical outcome in some patients.</p

Vasovagal tonus index (VVTI) as an indirect assessment of remission status in canine multicentric lymphoma undergoing multi-drug chemotherapy

Vasovagal tonus index (VVTI) is an indirect measure of heart rate variability and may serve as a marker of disease severity. Higher heart rate variability has predicted lower tumour burden and improved survival in humans with various tumour types. The purpose of this pilot study was to evaluate VVTI as a biomarker of remission status in canine lymphoma. The primary hypothesis was that VVTI would be increased in dogs in remission compared to dogs out of remission. Twenty-seven dogs were prospectively enrolled if they had a diagnosis of intermediate to high-grade lymphoma and underwent multidrug chemotherapy. Serial electrocardiogram data were collected under standard conditions and relationships between VVTI, remission status and other clinical variables were evaluated. VVTI from dogs in remission (partial or complete) did not differ from dogs with fulminant lymphoma (naive or at time of relapse). Dogs in partial remission had higher VVTI than dogs in complete remission (p&nbsp;=&nbsp;0.021). Higher baseline VVTI was associated with higher subsequent scores (p&nbsp;&lt;&nbsp;0.001). VVTI also correlated with anxiety level (p&nbsp;=&nbsp;0.03). Based on this pilot study, VVTI did not hold any obvious promise as a useful clinical biomarker of remission status. Further investigation may better elucidate the clinical and prognostic utility of VVTI in dogs with lymphoma