Versican upregulation in Sézary cells alters growth, motility and resistance to chemotherapy
| Autor: | Kazuyasu Fujii, Reinhard Dummer, Maria B. Karpova, K Asagoe, O Georgiev, Mirjana Urosevic-Maiwald |
|---|---|
| Přispěvatelé: | University of Zurich, Urosevic-Maiwald, M |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Stromal cell Cell 2720 Hematology Blotting Western 610 Medicine & health Antineoplastic Agents Apoptosis Real-Time Polymerase Chain Reaction Immunoenzyme Techniques Versicans Downregulation and upregulation Cell Movement medicine Biomarkers Tumor Tumor Cells Cultured Humans Sezary Syndrome 1306 Cancer Research RNA Messenger Sezary Cell Cell Proliferation Oligonucleotide Array Sequence Analysis biology Cell growth Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Cell Cycle 10177 Dermatology Clinic Hematology Cell cycle Lymphoma T-Cell Cutaneous carbohydrates (lipids) Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cell culture Drug Resistance Neoplasm Immunology biology.protein Cancer research Versican 2730 Oncology |
| Zdroj: | Leukemia. 29(10) |
| ISSN: | 1476-5551 |
| Popis: | Sezary syndrome (SeS) represents a leukemic variant of cutaneous T-cell lymphoma, whose etiology is still unknown. To identify dyregulated genes in SeS, we performed transcriptional profiling of Sezary cells (SCs) obtained from peripheral blood of patients with SeS. We identified versican as the highest upregulated gene in SCs. VCAN is an extracellular matrix proteoglycan, which is known to interfere with different cellular processes in cancer. Versican isoform V1 was the most commonly upregulated isoform in SCs. Using a lentiviral plasmid, we overexpressed versican V1 isoform in lymphoid cell lines, which altered their growth behavior by promoting formation of smaller cell clusters and by increasing their migratory capacity towards stromal cell-derived factor 1, thus promoting skin homing. Versican V1 overexpression exerted an inhibitory effect on cell proliferation, partially by promoting activation-induced cell death. Furthermore, V1 overexpression in lymphoid cell lines increased their sensitivity to doxorubicin and gemcitabine. In conclusion, we confirm versican as one of the dysregulated genes in SeS and describe its effects on the biology of SCs. Although versican overexpression confers lymphoid cells with increased migratory capacity, it also makes them more sensitive to activation-induced cell death and some chemotherapeutics, which could be exploited further for therapeutic purposes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|