Opticin, a small leucine-rich proteoglycan, is uniquely expressed and translocated to the nucleus of chronic lymphocytic
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Experimental Hematology & Oncology
RESEARCH
Open Access
Opticin, a small leucine-rich proteoglycan, is uniquely expressed and translocated to the nucleus of chronic lymphocytic leukemia cells Eva Mikaelsson1*, Anders Österborg1,2, Zahra Tahmasebi Fard7, Ahmad Mahmoudi3, Jafar Mahmoudian3, Mahmood Jeddi-Tehrani1,3, Mehdi Akhondi4, Fazel Shokri3,5, Paul N Bishop6, Hodjattallah Rabbani3 and Håkan Mellstedt1,2
Abstract Background: Opticin (OPTC) is a member of the small leucine-rich proteoglycan (SLRP) family and is localized particularly in certain extracellular matrices. We have previously reported the unique expression of another SLRP, fibromodulin (FMOD) in the leukemic cells of patients with chronic lymphocytic leukemia (CLL). OPTC is located in the same region as FMOD on chromosome 1 (1q32.1). Cluster up-regulation of genes may be observed in malignancies and the aim of the present study was to analyze the expression of OPTC in CLL cells. Methods: The expression of OPTC was tested by RT-PCR and realtime qPCR in PBMC from CLL patients, other hematological malignancies and healthy controls. The presence of OPTC protein, and its subcellular localization, was investigated using fractionation methods where the obtained lysate fractions were analyzed by Western blotting. Deglycosylation experiments were performed to investigate the glycosylation status of the CLL OPTC. Results: OPTC was expressed at the gene level in all patients with CLL (n = 90) and in 2/8 patients with mantle cell lymphoma (MCL) but not in blood mononuclear cells of healthy control donors (n = 20) or in tumor samples from nine other types of hematological malignancies. OPTC was detected by Western blot in all CLL samples analyzed (n = 30) but not in normal leukocytes (n = 10). Further analysis revealed a CLL-unique unglycosylated 37 kDa core protein that was found to be located preferentially in the cell nucleus and endoplasmic reticulum (ER) of the CLL cells. Conclusions: A 37 kDa unglycosylated OPTC protein was detected in ER and in the nucleus of CLL cells and not in healthy control donors. The function of this OPTC core protein remains unclear but its CLL-specific expression and subcellular localization warrants further investigations in the pathobiology of CLL. Keywords: Chronic lymphocytic leukemia, Opticin, Nucleus, Core protein, Proteoglycans
Introduction Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and has a highly variable clinical course. It is characterized by an accumulation of B cells expressing the cell surface antigens CD5, CD19, CD23, CD20dim and sIgMdim. In the last years, there has been an increased interest to characterize cellular and molecular
* Correspondence: [email protected] 1 Immune and Gene Therapy Lab, CCK, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden Full list of author information is available at the end of the article
mechanisms involved in the CLL biology with the aim to develop new targeted therapeutics [1,2]. In a study by Klein et al., the global gene
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