Ola Myklebost

Dr. Ola Myklebost– Assistant Director
Molecular characterization of mesenchymal cancer development
Dept. of Tumor Biology
Institute for Cancer Research
Oslo University Hospital,
The Norwegian Radium Hospital
ola.myklebost@imbv.uio.no
Tel +47 22 78 17 79


 

ACTIVITIES

The Mesenchymal Cancer Biology Group are studying sarcomas, malignant tumours with mesenchymal characteristics, and focus on osteo- and liposarcomas, as well as normal mesenchymal stem cells as model systems. Our CAST projects involve identification and characterization of stem-like cells in sarcomas, and the involvement of stem cell pathways in sarcoma development.

 

GROUP MEMBERS

Anna-Berit Wennerström
Technical personnel

Leonardo A. Meza-Zepeda
Senior Scientist

Menaka Sathermugathevan
Technical personnel

Petros Gebregziabher
Technical personnel

Russel Castro
Technical personnel

Stine Kresse
Post doc

Silje Lauvrak
Post doc


STATUS 2013

The microRNA let-7 is considered a tumor suppressor
and a regulator of stemness and differentiation, and is
normally highly expressed in well differentiated tissues.
The expression of let-7 is frequently lost in cancer, which has prognostic value in a wide range of cancers, and
let-7 replacement therapy shows great potential as a 
cancer therapeutic.

To date let-7 isoforms have not been fully characterized in sarcoma, so we are focused on determining expression level in a panel of liposarcoma cell lines. We are also investigating the effect of introducing let-7 mimics in chosen LPS cell line models to study the effects on growth rate, cell stemness and differentiation, in order to evaluate whether let-7 replacement therapy is also beneficial as therapy for sarcoma. We also examine the role of let-7 miRNAs in aggressive breast cancer cells, and found that they reduce cell growth as well as the cells capacity to generate spheroids in vitro. Furthermore, we have performed global analyses of the transcriptome and the proteome to identify changes that may explain these functional effects. In parallel, we have also analyzed the global effects of reducing the let-7 target gene HMGA2, which is an embryonic gene encoding an architectural transcription factor that is associated with the stemness program.

The comparisons identified some interesting differences that may enlighten processes involved in the balances between cell stemness and differentiation. Wnt/β-catenin signaling is frequently up-regulated in osteosarcoma and is thought to contribute to the disease. We have evaluated the effect of tankyrase inhibitors JW74 and JW55 on osteosarcoma cell lines, both at the molecular level and at the functional level. Interestingly, we have shown that the drug has the ability to induce differentiation in cell lines which have a block towards differentiation, thus enabling poorly differentiated cancer cells to overcome their resistance to differentiation, which may render the cells more susceptible for standard therapies.

 

SELECTED PUBLICATIONS

Sandberg CJAltschuler GJeong JStrømme KKStangeland BMurrell WGrasmo-Wendler UHMyklebost OHelseth EVik-Mo EOHide WLangmoen IA
Comparison of glioma stem cells to neural stem cells from the adult human brain identifies dysregulated Wnt- signaling and a fingerprint associated with clinical outcome
Exp Cell Res (in press)
PubMed 23791939

Stratford EWBostad MCastro RSkarpen EBerg KHøgset AMyklebost OSelbo PK (2013)
Photochemical internalization of CD133-targeting immunotoxins efficiently depletes sarcoma cells with stem-like properties and reduces tumorigenicity
Biochim Biophys Acta1830 (8)4235-43
PubMed 23643966

Bianchini LBirtwisle LSaâda EBazin ALong ERoussel JFMichiels JFForest FDani CMyklebost OBirtwisle-Peyrottes IPedeutour F (2013)
Identification of PPAP2B as a novel recurrent translocation partner gene of HMGA2 in lipomas
Genes Chromosomes Cancer52 (6)580-90
PubMed 23508853

Kuijjer MLPeterse EFvan den Akker BEBriaire-de Bruijn IHSerra MMeza-Zepeda LAMyklebost OHassan ABHogendoorn PCCleton-Jansen AM (2013)
IR/IGF1R signaling as potential target for treatment of high-grade osteosarcoma
BMC Cancer13245
PubMed 23688189

Doorn JFernandes HALe BQvan de Peppel Jvan Leeuwen JPDe Vries MRAref ZQuax PHMyklebost OSaris DBvan Blitterswijk CAde Boer J (2013)
A small molecule approach to engineering vascularized tissue
Biomaterials34 (12)3053-63
PubMed 23369216

Ohnstad HOCastro RSun JHeintz KMVassilev LTBjerkehagen BKresse SHMeza-Zepeda LAMyklebost O (2013)
Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma
Cancer119 (5)1013-22
PubMed 23165797

Skotheim RIMeza-Zepeda LAHovig ELønning PELothe RAMyklebost O (2012)
[Genome sequencing for personalized cancer treatment]
Tidsskr Nor Laegeforen132 (21)2406-8
PubMed 23160594

Kresse SHRydbeck HSkårn MNamløs HMBarragan-Polania AHCleton-Jansen AMSerra MLiestøl KHogendoorn PCHovig EMyklebost OMeza-Zepeda LA(2012)
Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma
PLoS One7 (11)e48262
PubMed 23144859

Namløs HMMeza-Zepeda LABarøy TØstensen IHKresse SHKuijjer MLSerra MBürger HCleton-Jansen AMMyklebost O (2012)
Modulation of the osteosarcoma expression phenotype by microRNAs
PLoS One7 (10)e48086
PubMed 23133552

Stratford EWCastro RDaffinrud JSkårn MLauvrak SMunthe EMyklebost O (2012)
Characterization of liposarcoma cell lines for preclinical and biological studies
Sarcoma2012148614
PubMed 22911243

Kuijjer MLRydbeck HKresse SHBuddingh EPLid ABRoelofs HBürger HMyklebost OHogendoorn PCMeza-Zepeda LACleton-Jansen AM (2012)
Identification of osteosarcoma driver genes by integrative analysis of copy number and gene expression data
Genes Chromosomes Cancer51 (7)696-706
PubMed 22454324

Skårn MNamløs HMNoordhuis PWang MYMeza-Zepeda LAMyklebost O (2012)
Adipocyte differentiation of human bone marrow-derived stromal cells is modulated by microRNA-155, microRNA-221, and microRNA-222
Stem Cells Dev21 (6)873-83
PubMed 21756067

Namløs HMKresse SHMüller CRHenriksen JHoldhus RSæter GBruland OSBjerkehagen BSteen VMMyklebost O (2012)
Global gene expression profiling of human osteosarcomas reveals metastasis-associated chemokine pattern
Sarcoma2012639038
PubMed 22518090

Kresse SHMeza-Zepeda LAMachado ILlombart-Bosch AMyklebost O (2012)
Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations
Cancer118 (2)558-70
PubMed 21713766

Hjortland GOMeza-Zepeda LABeiske KRee AHTveito SHoifodt HBohler PJHole KHMyklebost OFodstad OSmeland SHovig E (2011)
Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma
BMC Cancer11455
PubMed 22014070

Kuijjer MLNamløs HMHauben EIMachado IKresse SHSerra MLlombart-Bosch AHogendoorn PCMeza-Zepeda LAMyklebost OCleton-Jansen AM (2011)
mRNA expression profiles of primary high-grade central osteosarcoma are preserved in cell lines and xenografts
BMC Med Genomics466
PubMed 21933437

Stratford EWCastro RWennerstrom AHolm RMunthe ELauvrak SBjerkehagen BMyklebost O (2011)
Liposarcoma Cells with Aldefluor and CD133 Activity have a Cancer Stem Cell Potential
Clin Sarcoma Res1 (1)8
PubMed 22612877

Ohnstad HOPaulsen EBNoordhuis PBerg MLothe RAVassilev LTMyklebost O (2011)
MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines
BMC Cancer11211:1-11
PubMed 21624110

Buddingh EPKuijjer MLDuim RABürger HAgelopoulos KMyklebost OSerra MMertens FHogendoorn PCLankester ACCleton-Jansen AM (2011)
Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents
Clin Cancer Res17 (8)2110-9
PubMed 21372215

Kresse SHOhnstad HOBjerkehagen BMyklebost OMeza-Zepeda LA (2010)
DNA copy number changes in human malignant fibrous histiocytomas by array comparative genomic hybridisation
PLoS One5 (11)e15378
PubMed 21085701

Mayordomo EMachado IGiner FKresse SHMyklebost OCarda CNavarro SLlombart-Bosch A (2010)
A tissue microarray study of osteosarcoma: histopathologic and immunohistochemical validation of xenotransplanted tumors as preclinical models
Appl Immunohistochem Mol Morphol18 (5)453-61
PubMed 20436344

Eide MBLiestøl KLingjaerde OCHystad MEKresse SHMeza-Zepeda LMyklebost OTrøen GAamot HVHolte HSmeland EBDelabie J (2010)
Genomic alterations reveal potential for higher grade transformation in follicular lymphoma and confirm parallel evolution of tumor cell clones
Blood116 (9)1489-97
PubMed 20505157

Kresse SHSzuhai KBarragan-Polania AHRydbeck HCleton-Jansen AMMyklebost OMeza-Zepeda LA (2010)
Evaluation of high-resolution microarray platforms for genomic profiling of bone tumours
BMC Res Notes3223
PubMed 20691109

Henriksen JStabell MMeza-Zepeda LALauvrak SAKassem MMyklebost O (2010)
Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells
BMC Cancer10329
PubMed 20576167

Tenstad ETourovskaia AFolch AMyklebost ORian E (2010)
Extensive adipogenic and osteogenic differentiation of patterned human mesenchymal stem cells in a microfluidic device
Lab Chip10 (11)1401-1409
PubMed 20386793

Ottaviano LSchaefer KLGajewski MHuckenbeck WBaldus SRogel UMackintosh Cde Alava EMyklebost OKresse SHMeza-Zepeda LASerra MCleton-Jansen AMHogendoorn PCBuerger HAigner TGabbert HEPoremba C (2010)
Molecular characterization of commonly used cell lines for bone tumor research: a trans-European EuroBoNet effort
Genes Chromosomes Cancer49 (1)40-51
PubMed 19787792

Lehne GGrasmo-Wendler UHBerner JMMeza-Zepeda LAAdamsen BLFlack AReiner AClausen OPHovig EMyklebost O (2009)
Upregulation of stem cell genes in multidrug resistant K562 leukemia cells
Leuk Res33 (10)1379-85
PubMed 19394083

Kresse SHOhnstad HOPaulsen EBBjerkehagen BSzuhai KSerra MSchaefer KLMyklebost OMeza-Zepeda LA (2009)
LSAMP, a novel candidate tumor suppressor gene in human osteosarcomas, identified by array comparative genomic hybridization
Genes Chromosomes Cancer48 (8)679-93
PubMed 19441093

Roman EMeza-Zepeda LAKresse SHMyklebost OVasstrand ENIbrahim SO (2008)
Chromosomal aberrations in head and neck squamous cell carcinomas in Norwegian and Sudanese populations by array comparative genomic hybridization
Oncol Rep20 (4)825-43
PubMed 18813824

Kresse SHSkårn MOhnstad HONamløs HMBjerkehagen BMyklebost OMeza-Zepeda LA (2008)
DNA copy number changes in high-grade malignant peripheral nerve sheath tumors by array CGH
Mol Cancer748
PubMed 18522746

Lyng HLando MBrøvig RSSvendsrud DHJohansen MGalteland EBrustugun OTMeza-Zepeda LAMyklebost OKristensen GBHovig EStokke T (2008)
GeneCount: genome-wide calculation of absolute tumor DNA copy numbers from array comparative genomic hybridization data
Genome Biol9 (5)R86
PubMed 18500990

Meza-Zepeda LANoer ADahl JAMicci FMyklebost OCollas P (2008)
High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence
J Cell Mol Med12 (2)553-63
PubMed 18419597

Müller CRPaulsen EBNoordhuis PPedeutour FSaeter GMyklebost O (2007)
Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A
Int J Cancer121 (1)199-205
PubMed 17354236

Francis PNamløs HMMüller CEdén PFernebro JBerner JMBjerkehagen BAkerman MBendahl POIsinger ARydholm AMyklebost ONilbert M (2007)
Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential
BMC Genomics873
PubMed 17359542

Kleivi KLind GEDiep CBMeling GIBrandal LTNesland JMMyklebost ORognum TOGiercksky KESkotheim RILothe RA (2007)
Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses
Mol Cancer62
PubMed 17201907


Ola Myklebost laboratory