My main research interests are in the field of tumour biology, particularly of oral carcinogenesis, focusing on the role of normal neighbouring cells on the invasive and self renewal properties of oral cancer cells. I am however, fascinated by the cell-to-cell interactions, such that I am currently involved in research projects looking at cell-to-cell interactions in normal human oral tissues as well, and between human cells and periodontal bacterial cells.
Oral pathology and tumour biology
- 2016. Phenotypic plasticity determines cancer stem cell therapeutic resistance in oral squamous cell carcinoma. EBioMedicine. 4: 138-145. doi: 10.1016/j.ebiom.2016.01.007
- 2016. Vimentin-mediated regulation of cell motility through modulation of beta4 integrin protein levels in oral tumor derived cells. International Journal of Biochemistry and Cell Biology. 70: 161-172. doi: 10.1016/j.biocel.2015.11.015
- 2016. Nano-TiO2 penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa models. Journal of Oral Pathology & Medicine. 46: 214-222. doi: 10.1111/jop.12469
- 2016. Gene expression and proteome analysis as sources of biomarkers in basal cell carcinoma. Disease Markers. 2016:9831237. 9 sider. doi: 10.1155/2016/9831237
- 2016. Integrin a11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression. Journal of Oral Pathology & Medicine. doi: 10.1111/jop.12493
- 2016. Establishment of 3D co-culture models from different stages of human tongue tumorigenesis: Utility in understanding neoplastic progression. PLoS ONE. 11:e0160615. doi: 10.1371/journal.pone.0160615
- 2016. Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes. Biomaterials. 95: 11-21. doi: 10.1016/j.biomaterials.2016.04.002
- 2016. Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds. Head and Neck. 38: E1177-E1187. doi: 10.1002/hed.24187
- 2016. In vivo host response and degradation of copolymer scaffolds functionalized with nanodiamonds and bone morphogenetic protein 2. Advanced Healthcare Materials. 5: 730-742. doi: 10.1002/adhm.201500723
- 2015. MicroRNAs as important players and biomarkers in oral carcinogenesis. BioMed Research International. 2015:186904. 10 sider. doi: 10.1155/2015/186904
- 2015. The low-affinity nerve growth factor receptor p75NTR identifies a transient stem cell-like state in oral squamous cell carcinoma cells. Journal of Oral Pathology & Medicine. 44: 410-419. doi: 10.1111/jop.12251
- 2015. S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma. BMC Cancer. 15:631. 14 sider. doi: 10.1186/s12885-015-1622-1
- 2014. Human oral cancer cells with increasing tumorigenic abilities exhibit higher effective membrane capacitance. Integrative Biology. 6: 545-554. doi: 10.1039/c3ib40255j
- 2014. Rapid adherence to collagen IV enriches for tumour initiating cells in oral cancer. European Journal of Cancer. 50: 3262-3270. doi: 10.1016/j.ejca.2014.09.010
- 2014. A co-culture model with brain tumor-specific bioluminescence demonstrates astrocytes-induced drug resistance in glioblastoma. Journal of Translational Medicine. 12:278. doi: 10.1186/s12967-014-0278-y
- 2013. Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma. Cancer Research. 73: 3888-3901. doi: 10.1158/0008-5472.CAN-12-4150
- 2013. In vitro reconstruction of human junctional and sulcular epithelium. Journal of Oral Pathology & Medicine. 42: 396-404. doi: 10.1111/jop.12005
- 2013. Identification of FOXM1-induced epigenetic markers for head and neck squamous cell carcinomas. Cancer. 119: 4249-4258. Publisert 2013-12-15. doi: 10.1002/cncr.28354
- 2013. The effects of CD44 down-regulation on stem cell properties of head and neck cancer cell lines. Journal of Oral Pathology & Medicine. 42: 682-690. doi: 10.1111/jop.12076
- 2013. Successful triple immuno enzymatic method employing primary antibodies from same species and same immunoglobulin subclass. European journal of histochemistry. 57: 143-150. doi: 10.4081/ejh.2013.e22
- 2013. Human bone marrow mesenchymal stem cells induce collagen production and tongue cancer invasion. PLoS ONE. 8. 15 sider. doi: 10.1371/journal.pone.0077692
- 2013. S100A14 interacts with S100A16 and regulates its expression in human cancer cells. PLoS ONE. 8. 10 sider. doi: 10.1371/journal.pone.0076058
- 2013. Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis. International Journal of Cancer. 132: 2095-2106. doi: 10.1002/ijc.27886
- 2012. Limited in-depth invasion of Fusobacterium nucleatum into in vitro reconstructed human gingiva. Archives of Oral Biology. 57: 344-351. doi: 10.1016/j.archoralbio.2011.09.015
- 2012. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer. Cancer Medicine. 1: 128-140. doi: 10.1002/cam4.24
- 2012. Time-dependent biological differences in molecular markers of high-grade urothelial cancer over 7 decades (ras proteins, pTEN, uPAR, PAI-1 and MMP-9). Virchows Archiv. 461: 541-551. doi: 10.1007/s00428-012-1323-y
- 2012. The use of salivary cytokines as a screening tool for oral squamous cell carcinoma: A review of the literature. Journal of Oral and Maxillofacial Pathology. 16(2): 256-261. doi: 10.4103/0973-029X.99083
- 2012. S100A14 inhibits proliferation of oral carcinoma derived cells through G1-arrest. Oral Oncology. 48: 219-225. doi: 10.1016/j.oraloncology.2011.10.001
- 2011. Coexpression and nuclear colocalization of metastasis-promoting protein S100A4 and p53 without mutual regulation in colorectal carcinoma. Amino Acids. 41: 875-884. doi: 10.1007/s00726-010-0514-6
- 2011. Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative. Cancer Research. 71: 5317-5326. doi: 10.1158/0008-5472.CAN-11-1059
- 2011. Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis. Analytical and Bioanalytical Chemistry. 401: 2455-2463. doi: 10.1007/s00216-011-5337-0
- 2011. S100A14 regulates the invasive potential of oral squamous cell carcinoma derived cell-lines in vitro by modulating expression of matrix metalloproteinases, MMP1 and MMP9. European Journal of Cancer. 47: 600-610. doi: 10.1016/j.ejca.2010.10.012
- 2011. MicroRNA Alterations and Associated Aberrant DNA Methylation Patterns across Multiple Sample Types in Oral Squamous Cell Carcinoma. PLoS ONE. 6. 11 sider. doi: 10.1371/journal.pone.0027840
- 2010. Adverse effects of Sudanese toombak vs. Swedish snuff on human oral cells. Journal of Oral Pathology & Medicine. 39: 128-140. doi: 10.1111/j.1600-0714.2009.00825.x
- 2010. Induction of Human Epithelial Stem/Progenitor Expansion by FOXM1. Cancer Research. 70: 9515-9526. doi: 10.1158/0008-5472.CAN-10-2173
- 2010. Normal and malignant epithelial cells with stem-like properties have an extended G2 cell cycle phase that is associated with apoptotic resistance. BMC Cancer. 10. 16 sider. doi: 10.1186/1471-2407-10-166
- 2010. Rapid adherence to collagen IV enriches for tumour initiating cells. European Journal of Cancer. 8: 124-124.
- 2010. Khat alters the phenotype of in vitro-reconstructed human oral mucosa. Journal of Dental Research. 89: 270-275. doi: 10.1177/0022034509354980
- 2009. Coexpression and nuclear colocalization of metastasis-promoting protein S100A4 and p53 without mutual regulation in colorectal carcinoma. Amino Acids. 37: 79-79.
- 2009. Adverse effects of Sudanese toombak vs Swedish snuff on human oral cells. Journal of Oral Pathology & Medicine. Publisert 2009-11-04. doi: 10.1111/j.1600-0714.2009.00825.x
- 2009. Enhanced self-renewal properties of transformed oral epithelial cells after interactions with stromal fibroblasts. Oral Oncology. 92-93. doi: 10.1016/j.oos.2009.06.194
- 2009. Fusobacterium nucleatum Enters Normal Human Oral Fibroblasts In Vitro. Journal of Periodontology. 80: 1174-1183. Publisert 2009-07-01. doi: 10.1902/jop.2009.090051
- 2009. Cancer progression is associated with increased expression of basement membrane proteins in three-dimensional in vitro models of human oral cancer. Archives of Oral Biology. 54: 924-931. doi: 10.1016/j.archoralbio.2009.07.004
- 2009. Early loss of mitochondrial inner transmembrane potential in khat-induced cell death of primary normal human oral cells. Toxicology. 263: 108-116. doi: 10.1016/j.tox.2009.06.024
- 2009. Khat Alters the Phenotype of in vitro-reconstructed Human Oral Mucosa. Journal of Dental Research. Publisert 2009-12-31. doi: 10.1177/0022034509354980
- 2009. Phenotypic and functional differences between oral carcinoma-associated fibroblasts and normal oral fibroblasts. Oral Oncology. 221-221. doi: 10.1016/j.oos.2009.06.586
- 2008. Epithelial stem cells and malignancy. Journal of Anatomy. 213: 45-51. doi: 10.1111/j.1469-7580.2008.00895.x
- 2008. Generation of skin and oral mucosa from mouse embryonic stem cells under the influence of regional specific components. Journal of Investigative Dermatology. 128: S145-S145.
- 2008. Tissue engineering of oral dysplasia. Journal of Pathology. 215: 280-289. doi: 10.1002/path.2360
- 2008. Khat induces G1-phase arrest and increased expression of stress-sensitive p53 and p16 proteins in normal human oral keratinocytes and fibroblasts. European Journal of Oral Sciences. 116: 23-30. doi: 10.1111/j.1600-0722.2007.00508.x
- 2008. Khat (Catha edulis) induces reactive oxygen species and apoptosis in normal human oral keratinocytes and fibroblasts. Toxicological Sciences. 103: 311-324. doi: 10.1093/toxsci/kfn044
- 2007. Khat inhibits proliferation of normal oral keratinocytes in monolayers and organotypic cultures. Oral Oncology. 2: 198-198. doi: 10.1016/S1744-7895(07)70498-4
- 2007. Dual effects of sodium lauryl sulphate on human oral epithelial structure. Experimental Dermatology. 16: 574-579. doi: 10.1111/j.1600-0625.2007.00567.x
- 2007. Oral squamous cell carcinoma cells inhibit the growth of normal oral keratinocytes: a putative mechanism for intraepithelial tumour expansion. Oral Oncology. 2: 73-73. doi: 10.1016/S1744-7895(07)70089-5
- 2007. Recapitulating the features of mild, moderate and severe dysplasia using keratinocytes derived from clinical lesions and artificial connective tissue supports. Oral Oncology. 2: 180-181. doi: 10.1016/S1744-7895(07)70441-8
- 2007. The changing face of p53 in head and neck cancer. International Journal of Oral and Maxillofacial Surgery. 36: 1123-1138. doi: 10.1016/j.ijom.2007.06.006
- 2006. Differentiation of oral epithelium is regulated by GM-CSF and KGF at early but not terminal stages. Journal of Oral Pathology & Medicine. 35: 417-417.
- 2006. Species-specific fibroblasts required for triggering invasiveness of partially transformed oral keratinocytes. American Journal of Pathology. 168: 1889-1897. doi: 10.2353/ajpath.2006.050843
- 2006. Cancer Stem Cells – New and Potentially Important Targets for the Therapy of Oral Squamous Cell Carcinoma. Oral Diseases. 12: 443-454. doi: 10.1111/j.1601-0825.2006.01264
- 2006. Effects of khat (Catha edulis) on normal human oral cells. Journal of Oral Pathology & Medicine. 35: 443-443.
- 2005. The role of Bcl-2 in apoptosis induced by khat (Catha edulis) in acute myeloid leukemia cell lines. Blood. 106: 195b-195b.
- 2005. The phenotype of in vitro reconstituted normal human oral epithelium is essentially determined by culture medium. Journal of Oral Pathology & Medicine. 34: 247-252.
- 2005. Fibroblast control on epithelial differentiation is gradually lost during <EM>in vitro</EM> tumor progression. Differentiation. 73: 134-141.
- 2005. Keratinocyte sensitivity to fibroblast-derived differentiation signals is gradually lost during in vitro tumour progression. Oral Oncology. 41;1: 150-150.
- 2005. Basement membrane proteins in step-wise in vitro culture models of oral cancer progression. Oral Oncology. 42;1: 150-150.
- 2004. Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells. British Journal of Cancer. 91: 1726-1726.
- 2003. Crucial effects of fibroblasts and keratinocyte growth factor on morphogenesis of reconstructed human oral epithelium. Journal of Investigative Dermatology. 121: 1479-1486.
- 2005. Epithelial-Mesenchymal Interactions in Normal and Neoplastic Human Oral Mucosa - A Study on in Vitro Organotypic Models. University of Bergen, Bergen. 86 sider.
- 2002. Proliferation and differentiation in organotypic serum free cultures of normal oral mucosa. 108-113. I:
- 2002. Oral Oncology.
“Epithelial-Mesenchymal Interactions in Normal and Neoplastic Human Oral Mucosa - Studies on in Vitro Organotypic Models” ISBN 82-8006-022-70, UoB, Norway, 2005
Publications in peer reviewed international journals:
1. Costea DE, Loro LL, Dimba EA, Vintermyr OK, Johannessen AC (2003): Crucial effects of fibroblasts and keratinocyte growth factor on morphogenesis of reconstituted human oral epithelium. J Invest Dermatol. 121(6):1479-86.
2. Dimba EA, Gjertsen BT, Bredholt T, Fossan KO, Costea DE, Francis GW, Johannessen AC,Vintermyr OK (2004): Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of
caspase-1 and -8 in human leukaemia cells. Br J Cancer. 91(9):1726-34.
3. Costea DE, Dimba AO, Loro LL, Vintermyr OK, Johannessen AC (2005): The phenotype of in vitro reconstituted normal human oral epithelium is essentially determined by culture medium. J
Oral Pathol Med. 34(4):247-52.
4. Costea DE, Johannessen AC, Vintermyr OK (2005): Fibroblast control on epithelial differentiation is gradually lost during in vitro tumor progression. Differentiation. 73(4):134-41.
5. Costea DE, Kulasekara K, Neppelberg E, Johannessen AC, Vintermyr OK (2006): Species-specific fibroblasts required for triggering invasiveness of partially transformed oral keratinocytes. Am J Pathol. 168(6):1889-97.
6. Costea DE, Tsinkalovsky O, Vintermyr OK, Johannessen AC, Mackenzie IC (2006): Cancer stem cells - new and potentially important targets for the therapy of oral squamous cell carcinoma. Oral Dis. 12(5):443-54. Review.
7. Neppelberg E, Costea DE, Vintermyr OK, Johannessen AC (2007): Dual effects of sodium lauryl sulphate on human oral epithelial structure. Exp Dermatol. 16(7):574-9.
8. Partridge M, Costea DE, Huang X (2007): The changing face of p53 in head and neck cancer. Int J Oral Maxillofac Surg. 36(12):1123-38. Review.
9. Costea DE (2007): Meeting students’ and supervisors’ expectations - findings from a pilot study done at Centre for International Health, University of Bergen; Bergen Open Research Archive (BORA).
10. Lukandu OM, Costea DE, Dimba EA, Neppelberg E, Bredholt T, Gjertsen BT, Vintermyr OK, Johannessen AC (2008): Khat induces G1-phase arrest and increased expression of stress-sensitive
p53 and p16 proteins in normal human oral keratinocytes and fibroblasts. Eur J Oral Sci. 116(1):23-30.
11. Lukandu OM, Costea DE, Neppelberg E, Johannessen AC, Vintermyr OK (2008): Khat (Catha edulis) induces reactive oxygen species and apoptosis in normal human oral keratinocytes and
fibroblasts. Toxicol Sci. 103(2):311-24.
12. Costea DE, Gammon L, Kitajima K, Harper L and Mackenzie IC (2008): Epithelial stem cells and malignancy. J Anat. 213(1):45-51.Review.
13. Gaballah K, Costea DE, Hills A, Gollin SM, Harrison P, Partridge M (2008): Tissue engineering of oral dysplasia, J Pathol, 215(3):280-9.
14. Dabija-Wolter G, Cimpan MR, Costea DE, Johannessen AC, Sornes S, Neppelberg E, Al-Haroni M, Skaug N, Bakken V (2009): Fusobacterium nucleatum enters normal human oral fibroblasts in vitro, J Periodontol., 80(7):1174-83.
15. Lukandu OM, Bredholdt T, Neppelberg E, Gjertsen BT, Johannessen AC , Vintermyr OK , Costea DE (2009):Early Loss of Mitochondrial Membrane Potential in Khat-Induced Cell Death of
Primary Normal Human Oral Cells, Toxicology, 263(2-3):108-16.
16. Kulasekara KK, Lukandu OM, Neppelberg E, Vintermyr OK , Johannessen AC, Costea DE (2009) Increased basement membrane protein expression during cancer progression and under stromal
influence in experimental three-dimensional models of human oral mucosa, Arch Oral Biol. e-pub ahead of print.
17. Lukandu OM, Neppelberg E, Vintermyr OK , Johannessen AC , Costea DE (2009): Khat alters the phenotype of in vitro reconstructed human oral mucosa, accepted to J Dent Res.
18. Costea DE, Lukandu OM, Bui L, Ibrahim MJ, Lygre R, Neppelberg E, Ibrahim SO, Vintermyr OK, Johannessen AC (2009): Adverse effects of Sudanese Toombak versus Swedish snuff on primary human oral cells, accepted to J Oral Pathol Med.
Main research project
· The role of normal neighbouring cells on invasive and self renewal properties of oral cancer cells
Collaborative research projects - directly related to the main project
· Characterization of normal, dysplastic and tumour associated fibroblasts and their interactions with early transformed keratinocytes (with prof. M Partridge, Oncology, King’s College, UK, and prof. T Salo and postdoc P Nyberg, University of Oulu, Finland)
· Sensitivity of oral and breast cancer stem cells to apoptotic cell death induced by therapeutic agents (with prof. IC Mackenzie, Stem Cell Initiative, QMUL,UK, and assoc.prof. K Kitajima, Niigata Dental School, Japan)
· Identification and isolation of cancer stem cells in oral and colon cancers (collaboration with assoc. prof. F Labeed, University of Surrey, UK, postdoc O Tsinkalovsky and prof. OD Lærum , The Gade Institute, assoc. prof. PØ Enger, Institute of Biomedicine, University of Bergen, Norway)
Collaborative research projects – affiliated to the main project
· Interactions between oral cells and periodontal pathogens (collaboration with prof. V Bakken at Department of Microbiology, University of Bergen, Norway)
· Cytotoxic effects of Catha Edulis on oral cells (collaboration with prof. BT Gjertsen, Department of Internal Medicine, University of Bergen, Norway)