Publikationsserver der RWTH Aachen University
Molekulare Steuerung des Mamma-Karzinom-Verhaltens durch das inflammatorische Zytokin MIF
Abstract
dc:descriptionMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and mediator of acute and chronic inflammatory diseases. MIF is overexpressed in various tumours and has been suggested as a molecular link between chronic inflammation and cancer. In the context of the present study we investigated the role of MIF in tumorigenesis of breast cancer. MIF was abundantly expressed in the non-invasive breast cancer cell lines MDA-MB-468 and ZR-75-1, but not in invasive MDA-MB-231 cells, which in turn expressed higher levels of the MIF-receptor CD74. These cells are markedly more sensitive to stimulation with exogenous, recombinant MIF by increasing their own level of MIF secretion. The interesting point was that exogenous MIF influences the endogenous MIF secretion in all cell types, so that there must be kind of a feedback loop via an autocrine loop. Functional assays showed that autocrine MIF promoted tumour cell proliferation, as indicated by blockade of MIF or CD74 in MDA-MB-231 and MDA-MB-468. Similar effects were investigated in adhesion assays. We demonstrated that MIF influences cell adhesion and especially adhesion in non-invasive MDA-MB-468 cells which could be blocked by anti-MIF or anti-CD74-antibodies. Surprisingly proliferation and adhesion of normal breast tissue cells could be influenced only very little by stimulation or blockade. Also MDA-MB-231 invasiveness was enhanced by exogenous MIF and thus the inflammatory cytokine probably activates matrix-metalloproteinases, which are involved in degradation of basement membrane. In following studies we correlated the expression of MIF with different histopathological parameters and received first hints that lower cytosolic MIF expression levels could be found in breast cancer patients with bad prognosis. We concluded that MIF plays an important role in tumorigenesis and invasive behaviour of breast cancer. Invasive tumour cells seem to develop more effective adaptation to MIF stimulation. Furthermore intracellular expression of MIF in breast cancer is beneficial, whereas extracellular MIF may play a pro-oncogenic role in promoting breast cancer cell-stroma interactions.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2009
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Verjans, Eva Maria
- Contributors dc:contributor
-
- Bernhagen, Jürgen
Subjects
dc:subject × 7Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger