The focus of the Tumor Invasion and Metastasis (TIM) junior research group lies on the motile behavior of tumor cells in the context of radiation therapy. The mechanisms of migration and invasion of tumor cells within tissues as well as tumor cell metastasis are investigated.
NCT/UCC Junior Research Group Tumor Invasion and Metastasis
Understanding cell motility and metastasis in radiation oncology
Current studies suggest a connection of radiation therapy and the motile capacity of tumor cells. Unclear are the mechanistic links and the underlying cellular and molecular processes. Unraveling these fundamental mechanisms in the context of radiation therapy is the primary aim of the research group and key to the development of novel therapeutic approaches.
Another major focus lies on the identification of specific tumor cell characteristics – so called biomarkers – as predictors of tumor cell escape from the primary site and the formation of distant metastasis. Further steps will aim at visualization and molecular targeting of invading and metastasizing tumor cells on top of sensitization to radiation therapy.
(A) Simplified scheme of tumor cell invasion and metastasis and inhibition of these processes by radiation therapy and novel therapeutics (B) Invasion of Glioblastoma cells from a multicellular spheroid (center) into a 3-dimensional collagen type-I matrix. (C) Immunofluorescent staining of invading Glioblastoma cells (blue: nucleus, green: actin cytoskeleton). Copyright: Anne Vehlow
The research group performs a variety of methods with a particular focus on cell culture techniques, molecular and biochemical assays and microscopy.
- Culture of cell lines and primary cells
- Cell motility and invasion assays
- Colony and sphere formation assays
- Assessment of cell proliferation and viability
- Apoptosis assay
- DNA damage analysis
- siRNA and gene transfection
- Molecular biology and cloning
- SDS-PAGE and Western blotting
- Signal transduction analysis
- Protein interaction analysis
- Mass spectrometry (in cooperation)
- Omics (in cooperation)
- Orthotopic tumor xenografts
Naumann M, Pal A, Goswami A, Lojewski X, Japtok J, Vehlow A, Naujock M, Günther R, Jin M, Stanslowsky N, Reinhardt P, Sterneckert J, Frickenhaus M, Pan-Montojo F, Storkebaum E, Poser I, Freischmidt A, Weishaupt JH, Holzmann K, Troost D, Ludolph AC, Boeckers TM, Liebau S, Petri S, Cordes N, Hyman AA, Wegner F, Grill SW, Weis J, Storch A, Hermann A. (2018). Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation. Nature Communications 9(1):335
Vehlow A, Klapproth E, Storch K, Dickreuter E, Seifert M, Dietrich A, Bütof R, Temme A, Cordes N (2017). Adhesion- and stress-related adaptation of glioma radiochemoresistance is circumvented by β1 integrin/JNK co-targeting. Oncotarget. 2017 Apr 27. doi: 10.18632/oncotarget.17480.
Vehlow A, Storch K, Matzke D, Cordes N. (2016). Molecular Targeting of Integrins and Integrin-Associated Signaling Networks in Radiation Oncology. Recent Results Cancer Res. 2016;198:89-106
Dickreuter E, Vehlow A, Cordes N (2015). 3D-Zellkultur zur Identifizierung von Zielmolekülen für die Krebstherapie. BIOspektrum 21(4):397-400.
Steglich A, Vehlow A, Eke I, Cordes N (2015). α integrin targeting for radiosensitization of three-dimensionally grown human head and neck squamous cell carcinoma cells. Cancer Letters 357(2):542-8.
Law AL, Vehlow A, Kotini M, Dodgson L, Soong D, Theveneau E, Bodo C, Taylor E, Navarro C, Perera U, Michael M, Dunn GA, Bennett D, Mayor R, Krause M (2013). Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo. Journal of Cell Biology 203(4):673-89
Vehlow A, Soong D, Vizcay-Barrena G, Bodo C, Law AL, Perera U, Krause M (2013). Endophilin, Lamellipodin, and Mena cooperate to regulate F-actin-dependent EGF-receptor endocytosis. EMBO Journal 32(20):2722-34
Vehlow A, Cordes N (2013). Invasion as target for therapy of glioblastoma multiforme. Biochimica et Biophysica Acta 1836(2):236-44
Eke I & Storch K, Kästner I, Vehlow A, Faethe C, Mueller-Klieser W, Taucher-Scholz G, Temme A, Schackert G, Cordes N (2012). Three-dimensional invasion of human glioblastoma cells remains unchanged by X-ray and carbon ion irradiation in vitro. International Journal of Radiation Oncology, Biology, Physics 84(4):515-23
Michael M, Vehlow A, Navarro C, Krause M (2010). C-Abl, Lamellipodin, and Ena/VASP proteins cooperate in dorsal ruffling of fibroblasts and axonal morphogenesis. Current Biology 20(9):783-91
Henderson RB, Grys K, Vehlow A, de Bettignies C, Zachacz A, Henley T, Turner M, Batista F, Tybulewicz VL (2010). A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival. Journal of Experimental Medicine 207(4):837-53
Lyulcheva E, Taylor E, Michael M, Vehlow A, Tan S, Fletcher A, Krause M and Bennett D (2008). Drosophila Pico and Its Mammalian Ortholog Lamellipodin Activate Serum Response Factor and Promote Cell Proliferation. Developmental Cell 15(5):680-690
Arana E* & Vehlow A*, Harwood NE, Vigorito E, Henderson R, Turner M, Tybulewicz VLJ and Batista FD (2008). Activation of the Small GTPase Rac2 via the B Cell Receptor Regulates B Cell Adhesion and Immunological-Synapse Formation. Immunity 28(1):88-99 *Co-first authors
Batista FD, Arana E, Barral P, Carrasco YR, Depoil D, Eckl-Dorna J, Fleire S, Howe K, Vehlow A, Weber M and Treanor B (2007). The role of integrins and coreceptors in refining thresholds for B-cell responses. Immunological Reviews 218:197-213