Integrins and Extracellular Matrix
in Tumor Biology

Principal investigatior                                                                                                                                                      

Prof. Dr. rer. nat. Dr. med. habil. Ute Reuning
Department of Gynecology and Obstetrics
Technical University of Munich
Clinical Research Unit
Tel.:  +49-89-4140 7407/2433
Fax: +49-89-4140 7410/4846
Email: ute.reuning@mri.tum.de(link sends e-mail)

Main research topics

• Effects of specific integrin-mediated cell adhesion on the tumor biological behaviour of human ovarian and breast cancer cells
• Differential gene expression in human cancer cells as a function of integrin αvβ3 expression
• Interaction of integrins with other cell surface receptors and signaling molecules (e.g. epidermal growth factor receptor, integrin-linked kinase)
• Characterisation of the role of the putative tumor suppressor ADAM15 in human ovarian cancer cells and its functional interaction with integrin αvβ3
• Characterisation of the role of the tetraspanin and tumor suppressor KAI1 (CD82) in concert with integrin αvβ3 in human ovarian and breast cancer cells
• Investigation of molecular mechanisms and conformational changes during integrin activation and integrin-mediated signal transduction
• Development, screening, and testing of specific integrin antagonists for therapeutical intervention
• Determination of integrin αvβ3 binding parameters to extracellular matrix proteins and synthetic (antagonistic) integrin ligands by surface plasmon spectroscopy on integrin-functionalized artificial phospholipid membranes
• Integrin/ligand binding assays using cell-free in vitro synthesized integrins on polymeric vesicular membrane architectures
• Isolation of circulating tumor cells from the blood of cancer patients by use of an antibody-functionalized nanodetector

Lectures

• Doctoral seminars in Gynecological Oncology
• Seminar for postgraduate researchers in Gynecology and Obstetrics
• Current topics in Molecular Medicine
• Supervision and instruction of graduate students and postdoctoral fellows in scientific work
• Seminar on Clinical and Biological Aspects of Breast and Ovarian Cancer
• Current Topics in Gynecological Oncology
• Seminar on Technical Aspects Related to Molecular Biology, Cell Biology, and Protein Biochemistry

Selected publications

Bronger, H., Singer, J., Windmüller, C., Reuning, U., Zech, D., Delbridge, C., Dorn, J., Kiechle, M., Schmalfeldt, B., Schmitt, M., Avril, S. CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition in advanced serous ovarian cancer. British Journal of Cancer, in press, 05 2016.

Maltsev, O. V., Marelli, U. K., Kapp, T. G., Di Leva, F. S., Di Maro, S., Nieberler, M., Reuning, U., Schwaiger, M., Novellino, E., Marinelli, L. & Kessler H. Stable peptides instead of stapled peptides: highly potent αvβ6-selective integrin ligands.(link is external) Angewandte Chemie International Edition (Engl.) 55: 1535-1539, 2016.

Zaba, C., Ritz, S., Tan, C.D., Zayni, S., Müller, M., Reuning, U. & Sinner, E. K. Functional cell adhesion receptors (integrins) in polymeric architectures.(link is external) Chembiochem 16: 1740-1743, 2015.

Upheber, S., Karle, A., Miller, J., Schlaugk, S., Gross, E., Reuning U. Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin αvβ3-mediated ovarian cancer biology.(link is external) Cellular Signalling 27: 652-662, 2015.

Seubert, B., Cui, H., Simonavicius, N., Honert, K., Schäfer, S., Reuning, U., Heikenwalder, M., Mari, B., Krüger, A. Tetraspanin CD63 acts as a pro-metastatic factor via β-catenin stabilization.(link is external) International Journal of Cancer 136: 2304-2315, 2015.

Iturri, J., García-Fernández, L., Reuning, U., Garcia, A., del Campo, A. & Salierno, M. Synchronized cell attachment triggered by photo-activatable adhesive ligands allows QCM-based detection of early integrin binding. Scientific Reports 5: 9533, 2015.

Cui, H., Seubert, B., Stahl, E., Dietz, H., Reuning, U., Nagase, H., Mari, B., Krüger, A. Tissue inhibitor of metalloproteinases-1 induces a pro-tumorigenic increase of miR-210 in lung adenocarcinoma cells and their exosomes. Oncogene 34: 3640-3650, 2015

Müller MA, Brunie L, Bächer AS, Kessler H, Gottschalk KE, Reuning U. Cytoplasmic salt bridge formation in integrin αvß3 stabilizes its inactive state affecting integrin-mediated cell biological effects.(link is external) Cellular Signalling 26: 2493-2503, 2014.

Volkmann, J., Reuning, U., Rudelius, M., Haefner, N., Schuster, T., Becker v. Rose, A., Weimer, J., Hilpert, F., Kiechle, M., Duerst, M., Arnold, N., Schmalfeldt, B., Meindl, A., Ramser, J. High expression of crystallin αB represents an independent molecular marker for unfavourable ovarian cancer patient outcome and impairs TRAIL- and cisplatin-induced apoptosis in human ovarian cancer cells. International Journal of Cancer 132: 2820-2832, 2013.

Neubauer, S., Rechenmacher, F., Beer, A. J., Curnis, F., Pohle, K., D'Alessandria, C., Wester, H. J., Reuning, U., Corti, A., Schwaiger, M., Kessler, H. Selective imaging of the angiogenic relevant integrins α5β1 and αvβ3.(link is external) Angewandte Chemie International Edition (Engl.) 52: 11656-11659, 2013.

Müller, M., Opfer, J., Brunie, L., Volkhardt, L. A., Sinner, E. K., Boettiger, D., Bochen, A., Kessler, H., Gottschalk, K. E., Reuning, U. The glycophorin A transmembrane sequence within αvβ3 creates a nonsignaling integrin with low basal affinity that is strongly adhesive under force.(link is external) Journal of Molecular Biology 425: 2988-3006, 2013.

Mas-Moruno, C., Dorfner, P. M., Manzenrieder, F., Neubauer, S., Reuning, U., Burgkart, R. & Kessler, H. Behavior of primary human osteoblasts on trimmed and sandblasted Ti6Al4V surfaces functionalized with integrin αvβ3-selective cyclic RGD peptides. Journal of Biomedical Materials Research-Part A: 101: 87-97, 2013.

Reuning, U. Integrin αvβ3 promotes vitronectin gene expression in human ovarian cancer cells by implicating rel transcription factors.(link is external) Journal of Cellular Biochemistry 112: 1909-1919, 2011.

Preissner, K. T. & Reuning, U. Vitronectin in vascular context: facets of a multitalented matricellular protein.(link is external) Seminars in Thrombosis and Hemostasis 37: 408-424, 2011.

Ruseva, Z., Geiger, P.X.C., Hutzler, P., Kotzsch, M., Luber, B., Schmitt, M., Groß, E. & Reuning, U. Tumor suppressor KAI1 affects integrin αvß3-mediated ovarian cancer cell adhesion, motility and proliferation. Experimental Cell Research 315: 1759-1771, 2009.

Lössner, D., Abou-Ajram, C., Benge, A., Aumercier, M., Schmitt, M. & Reuning, U. Integrin avß3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription.(link is external) Journal of Cellular Physiology 220: 367-375, 2009.

Lössner, D., Abou-Ajram, C., Benge, A. & Reuning, U. Integrin avß3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells.(link is external) International Journal of Biochemistry and Cell Biology 40: 2746-2761, 2008.

Lössner, D., Kessler, H., Thumshirn, G., Dahmen, C., Wiltschi, B., Tanaka, M., Knoll, W., Sinner, E. K. & Reuning, U. Binding of small mono- and oligomeric integrin ligands to membrane-embedded integrins monitored by surface plasmon-enhanced fluorescence spectroscopy. Analytical Chemistry 78: 4524-4533, 2006.

Krupka, S. S., Wiltschi, B., Reuning, U., Hölscher, K., Hara, M. & Sinner, E.-K. In vivo detection of membrane protein expression using surface plasmon enhanced fluorescence spectroscopy (SPFS). Biosensors & Bioelectronics 22: 260-267, 2006.

Li, J., Thielemann, C., Pax, M., Reuning, U. & Johannsmann, D. Monitoring of integrin-mediated adhesion of human ovarian cancer cells to model protein surfaces by quartz crystal resonators: evaluation in the impedance analysis mode. Biosensors & Bioelectronics 20: 1333-1340, 2005.

Beck, V., Herold, H., Benge, A., Luber, B., Hutzler, P., Tschesche, H., Kessler, H., Schmitt, M., Geppert, H. G. & Reuning, U. ADAM15 decreases integrin avß3/vitronectin-mediated ovarian cancer cell adhesion and motility in an RGD-dependent fashion. International Journal of Biochemistry and Cell Biology 37: 590-603, 2005.

A complete list of publications can be found here(link is external).

Grants

• Deutsche Forschungsgemeinschaft (DFG)
• Bundesministerium für Bildung und Forschung (BMBF)
• Deutsche Krebshilfe
• Kommission für Klinische Forschung an der Medizinischen Fakultät der Technischen Universität München
• Forschungsstipendien des Frauenbüros der TUM "Chancengleichheit für Frauen und Forschung und Lehre"
  
  

Dissertation/Scientific work

If you are interested in writing an experimental thesis (Dr. rer. nat., Dr. med.) please contact Prof. Dr. U. Reuning.