Laboratory for Cell Biology and Signalling

Laboratory for Cell Biology and Signalling

Laboratory for cell biology and signalling (LCBS) explores biological processes in human tumour cells triggered by antitumor drugs or newly synthesised compounds with the aim to improve the tumour therapy. In addition, we investigate biology of adenovirus vectors, as a gene transfer tools for further use in tumour gene therapy and vaccination.  We utilise the methods of cell and molecular biology, biochemistry and advanced light microscopy.

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Research objectives:

  1. Integrin-mediated signalling pathways in tumour cells upon exposure to antitumour drugs and metastasis.
  2. Molecular mechanisms of drug resistance in tumour cells with an emphasis on the role of miRNA and integrins in these processes.
  3. Newly synthesised compounds as potential antitumor drugs.
  4. Adenovirus vectors as tools for gene transfer and vaccination.

Research groups:

Ambriović Ristov Group

Group Ambriović-Ristov investigates signalling pathways in tumour cells triggered by integrins and the potential of modulation of integrin expression for sensitisation of tumour cells to antitumor drugs. In addition, we study the role of integrins in cell migration and invasion. We are interested in focal adhesions, defined as a type of adhesive contact between the cell and extracellular matrix, their composition, formation and evolution in living cells during spreading or migration.

Brozović Group

The major problems of successful chemotherapy are development of drug resistance and side effects. Brozovic group is focused on molecular mechanisms involved in drug resistance of tumour cells especially on the role of miRNAs and correlation between epithelial-mesenchymal transition and drug resistance. Further, in order to improve the success of chemotherapy, Brozovic group is investigating the biological effects of newly synthesised compounds, the organometallic complexes.

Majhen Group

Adenovirus based vectors have potential translational and commercial values and are currently studied as vectors for gene transfer and vaccination. In Majhen group we study the basic biology of adenoviral vectors, namely adenovirus type 5 and 26. The main objective of our study is finding a link between binding of the adenoviral vector to the receptor on the cell surface, its intracellular trafficking and induction of immune response of the infected cell. Our research interest is also retargeting of adenoviral vectors toward molecule of interest and studying intracellular trafficking of retargeted adenoviral vectors.

Featured publication

2016

  • Ruščić J, Ambriović-Ristov A, Majhen D, Kolundžija S, Barut M, Benihoud K, Krajačić M. Manipulating adenoviral vector ion-exchange chromatography: Hexon versus fiber. J Sep Sci. 2016. in press
  • Christmann M., Diesler K., Majhen D., Steigerwald C., Berte N., Freund H., Stojanović N., Kaina B., Osmak M., Ambriović-Ristov A., Tomicic MT. Integrin αVβ3 silencing sensitizes malignant glioma cells to temozolomide by suppression of homologous recombination repair. Oncotarget,  2016. in press
  • Stojanović N., Brozovic A., Majhen D., Bosnar M.H., Fritz G., Osmak M., Ambriović-Ristov A. Integrin αvβ3 expression in tongue squamous carcinoma cells Cal27 confers anticancer drug resistance through loss of pSrc(Y418). Biochimica et Biophysica Acta. 1863(8):1969-78. 2016.
  • Steiner I.*, Stojanović N.*, Bolje A., Brozovic A., Polančec D., Ambriović-Ristov A., Radić Stojković M., Piantanida I, Eljuga D., Košmrlj J., Osmak M. Discovery of ‘click’ 1,2,3-triazolium salts as potential anticancer drugs – Radiology and Oncology, 2016. in press  *equal contribution

2014-2015

  • Brozovic A., Duran G.E., Wang Y.C., Francisco B.E., Sikic B.I. The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells. Molecular Oncology. 9(8):1678-93., 2015.
  • Vajs J.*, Steiner I.*, Brozovic A.*, Pevec A., Ambriović-Ristov A., Matković M., Piantanida I., Urankar D., Osmak M., Košmrlj J. The 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes with a high in vitro anticancer activity. J Inorg Biochem. 153:42-8. 2015. *equal contribution
  • Krüger K., Thomale J., Stojanovic N., Osmak M., Henninger C., Bormann S., Fritz G. Platinum-induced kidney damage: Unraveling the DNA damage response (DDR) of renal tubular epithelial and glomerular endothelial cells following platinum injury. Biochimica et Biophysica Acta. 1853: 685-698, 2015.
  • Murati T., Šimić B., Brozovic A., Kniewald J., Miletić Gospić A., Bilandžić N., Kmetič I. PCB 77 action in ovary cells--toxic effects, apoptosis induction and cell cycle analysis. Toxicology Mechanisms and Methods. 25(4): 302-11., 2015.
  • Majhen D., Calderon H., Chandra N., Fajardo C.A., Rajan A., Alemany R., Custers J. Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field.Human Gene Therapy. 25, 301-317, 2014.
  • Majhen D., Stojanović N., Vukić D., Pichon C., Leduc C., Osmak M., Ambriović-Ristov A. Increased Adenovirus Type 5 Mediated Transgene Expression Due to RhoB Down-regulation, PLoS One. 9(1): e86698, 2014.
  • Moisan F., Francisco E.B., Brozovic A., Duran G.E., Wang Y.C., Chaturvedi S., Seetharamb S., Snyder L.A., Doshi P., Sikic B.I. Enhancement of Paclitaxel and Carboplatin Therapies by CCL2 Blockade in Ovarian Cancers. Molecular Oncology. 8: 1231-1239, 2014.
  • Rak S., De Zan T., Štefulj J., Kosović M., Gamulin O., Osmak M. FTIR spectroscopy reveals lipid droplets in drug resistant laryngeal carcinoma cells through detection of increased ester vibrational bands intensity. Analyst. 139, 13: 3407-3415, 2014.
  • Sommer M., Kureljak P., Urankar D., Schweinfurth D., Stojanović N., Bubrin M., Gazvoda M., Osmak M., Sarkar B., Košmrlj J. Combining [Arene–Ru] with Azocarboxamide to Generate a Complex with Cytotoxic Properties. Chemistry: A European Journal, Communication. 20: 17296-17299, 2014.
  • Vellinga J., Smith J.P., Lipiec A., Majhen D., Lemckert A., van Ooij M., Ives P., Yallop C., Custers J., Havenga M. Challenges in manufacturing adenoviral vectors for global vaccine product deployment. Human Gene Therapy. 25: 318-327, 2014.

 

2012-2013

  • Brozovic A., Vuković L., Polančac D.S., Arany I., Köberle B., Fritz G., Fiket Z., Majhen D., Ambriović-Ristov A., Osmak M. Endoplasmic reticulum stress is involved in the response of human laryngeal carcinoma cells to carboplatin but is absent in carboplatin-resistant cells. PLoS One. 8(9): e76397, 2013.
  • Rak S., Čimbora-Zovko T., Gajski G., Dubravčić K., Domijan A., Delaš I., Garaj-Vrhovac V., Batinić D.,  Sorić J., Osmak M. Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation. Toxicology In Vitro. 27, 2; 523-532, 2013.
  • Watanabe S., De Zan T., Ishizaki T., Yasuda S., Kamijo H., Yamada D., Aoki T., Kiyonari H., Kaneko H., Shimizu R., Yamamoto M., Goshima G., Narumiya S. Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis. Cell Reports. 20135:926-932, 2013. 
  • Watanabe S., De Zan T., Ishizaki T., Narumiya S. Citron kinase mediates transition from constriction to abscission through its coiled-coil domain. Journal of Cell Science. 126:1773-84, 2013.
  • Gabrilovac J., Čupić B., Zapletal E., Brozović A. IFN-γ up-regulates kappa opioid receptors (KOR) on murine macrophage cell line J774. Journal of Neuroimmunology. 245, 1/2; 56-65, 2012.
  • Majhen D., Richardson J., Vukelić B., Dodig I., Cindrić M., Benihoud K., Ambriović-Ristov A. The disulfide bond of an RGD4C motif inserted within the HI loop of the adenovirus type 5 fiber protein is critical for retargeting to αv-integrins. Journal of Gene Medicine. 14(12): 788-797, 2012.
  • Osmak M. Statins and cancer: Current and future prospects. Cancer Letters. 324, 1; 1-12, 2012.

 

2010-2011

  • Čimbora-Zovko T., Brozović A., Piantanida I., Fritz G., Virag A., Alič B., Majce V., Kočevar M., Polanc S., Osmak M. Synthesis and biological evaluation of 4-nitro-substituted 1, 3-diaryltriazenes as a novel class of potent antitumor agents. European Journal of Medicinal Chemistry. 46: 2971-2983, 2011.
  • Gabrilovac J., Čupić B.,Živković E., Horvat L., Majhen D. Expression, regulation and functional activities of aminopeptidase N (EC 3.4.11.2 ; APN ; CD13) on murine macrophage J774 cell line. Immunobiology. 216, 1/2; 132-144, 2011.
  • Helbig L., Damrot J., Hülsenbeck J., Köberle B., Brozović A., Osmak M., Fiket Ž., Kaina B., Fritz G. Late activation of stress-activated protein kinases/C-JUN-N- terminal kinases triggered by cisplatin-induced DNA damage repair defective cells. The Journal of Biological Chemistry. 286, 15; 12991-13001, 2011.
  • Majhen D., Stojanović N., Špeljko T., Brozović A., De Zan T., Osmak M., Ambriović-Ristov A. Increased expression of the coxsackie and adenovirus receptor downregulates alpha v beta 3 and alpha v beta 5 integrin expression, reduces cell adehesion and migration. Life Sciences. 89: 241-249, 2011.
  • Brozovic A., Ambriović-Ristov A., Osmak M. The relationship between cisplatin-induced reactive oxygen species, glutathione and BCL-2, and resistance to cisplatin. Critical Reviews in Toxicology. 40(4): 347-359, 2010.
  • Majhen D*, Brozovic A*, Buger T, Gabrilovac J, Osmak M, Ambriović-Ristov A. Vincristine-resistant human laryngeal carcinoma cells demonstrate increased Rous sarcoma virus promoter activity. Life Sciences. 87(15-16):468-474, 2010.  *equal contribution
  • Burja B., Čimbora-Zovko T., Tomić S., Jelušić T., Kočevar M., Polanc S., Osmak M. Pyrazolone-fused combretastatins and their precursors: synthesis, cytotoxicity, antitubulin activity and molecular modeling studies. Bioorganic & Medicinal Chemistry. 18: 2375-2387, 2010.
  • Cimbora-Zovko T., Fritz G., Mikac N., Osmak M. Downregulation of RhoB GTPase confers resistance to cisplatin in human laryngeal carcinoma cells. Cancer Letters.  295:182-190, 2010.

 

2008-2009

  • Brozović A., Damrot J., Tsaryk R., Helbig L., Nikolova T., Hartig C., Osmak M., Roos W., Kaina B., Fritz G. Cisplatin sensitivity is related to late DNA damage processing and checkpoint control rather than to the early DNA damage response. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 670, 1-2; 32-41, 2009.
  • Majhen D., Nemet J., Richardson J., Gabrilovac J., Hajsig M., Osmak M., Eloit M., Ambriović-Ristov A. Differential role of αvβ3 and αvβ5 integrins in internalization and transduction efficacies of wild type and RGD4C fiber-modified adenoviruses. Virus Research. 139(1): 64-73, 2009.
  • Brozović A., Majhen D, Roje V., Mikac N., Jakopec S., Fritz G., Osmak M., Ambriović-Ristov A. αvβ3 integrin mediated drug resistance in human laryngeal carcinoma cells is caused by glutathione dependent elimination of drug induced reactive oxidative species. Molecular Pharmacology. 74: 298-306, 2008.

 

2006-2007

  • Brozović A., Osmak M. Activation of mitogen-activated protein kinases by cisplatin and their role in cisplatin-resistance. Cancer Letters. 251 (2007), 1; 1-16, 2007.
  • Čimbora-Zovko T., Ambriović-Ristov A.; Lončarek J., Osmak M.: Altered cell-cell adhesion in cisplatin-resistant human carcinoma cells: A link between b-catenin/plakoglobin ratio and cisplatin resistance. European Journal of Pharmacology. 558: 27-36, 2007.
  • Zisowsky J., Koegel S., Leyers S., Devarakonda K., Kassack M., Osmak M., Jaehde U. Relevance of drug uptake and efflux for platinum sensitivity of tumour cells. Biochemical Pharmacology. 73, 2; 298-307, 2007.
  • Jakopec S., Dubravčić K., Polanc S., Košmrlj J., Osmak M.: Diazene JK-274 induces apoptosis-like cell death in human cervical carcinoma cells. Toxicology In Vitro. 20:217-226, 2006.
  • Majhen D., Ambriović-Ristov, A. Adenoviral vectors-how to use them in cancer gene therapy, Virus Research. 119: 121-133, 2006.
  • Majhen D., Gabrilovac J., Eloit M., Richardson J., Ambriović-Ristov A. Disulfide bond formation in NGR fiber-modified adenovirus is essential for retargeting to aminopeptidase N. Biochemical and Biophysical Research Communications. 348: 278-287, 2006.

Ana Dekanić

+385 1 456 1145
1545 1876

Anamaria Brozović
PhD

Senior Associate Scientist
+385 1 456 1145
1545 1877

Andreja Ambriović Ristov
Ph.D.

Senior Scientist
+385 1 457 1240
1543 1545

Dragomira Majhen
dr.sc.

research associate
+385 1 456 1145
1545 1876

Mladen Paradžik
B.Sc.

PhD student
+385 1 456 1145
1545 1876

Nikolina Stojanović
PhD

senior research assistant
+385 1 456 1145
1545 1876

Sanjica Rak
PhD

Assistant
+385 1 457 1293
1545 1305

Tihana De Zan
B. Sc.

Research Fellow, Assistant
+385 1 456 1145
1545 1305