Related Experiment Video
Updated: May 23, 2026
Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
Published on: March 26, 2018
Aberrant calreticulin expression is involved in the dedifferentiation of dedifferentiated liposarcoma
Masanori Hisaoka1, Atsuji Matsuyama, Mitsuhiro Nakamoto
1Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. hisaoka@med.uoeh-u.ac.jp
Abstract:
Liposarcomas are a representative group of soft tissue sarcomas with variably hampered adipogenesis, which is most exemplified by its dedifferentiated subtype. However, the factor(s) responsible for inhibiting adipocyte differentiation remains unknown. A recent gene expression profiling study identified several unique genes that were highly expressed in dedifferentiated liposarcoma, and the gene encoding calreticulin (CALR), a major Ca(2+)-buffering protein that can inhibit adipocyte differentiation, was found to be overexpressed. Thus, we investigated the expression of calreticulin in 45 cases of liposarcomas, including 15 dedifferentiated tumors, at both the protein and mRNA levels. Immunohistochemically, calreticulin was consistently expressed in the dedifferentiated areas of dedifferentiated liposarcomas and commonly observed in atypical stromal cells and/or lipoblasts in the well-differentiated areas (87%), whereas large vacuolated adipocytic cells in either the tumors or normal fat were essentially negative. These results were further supported by the findings of Western blot and quantitative RT-PCR analyses. Although abnormalities in 19p13.1-13.2 where CALR is localized were uncommon in the dedifferentiated liposarcomas examined by fluorescence in situ hybridization, expression of miR-1257, a putative microRNA that targets calreticulin, was suppressed in the dedifferentiated subtype. The down-regulation of calreticulin by small-interfering RNA could induce adipogenesis in dedifferentiated liposarcoma cells and reduce cell proliferation. Our results therefore suggest that aberrantly expressed calreticulin in dedifferentiated liposarcoma is involved in its dedifferenitation and/or tumor progression.
Insights
Aberrantly expressed calreticulin (CALR) inhibits adipocyte differentiation in dedifferentiated liposarcoma. Suppressing CALR promotes adipogenesis and reduces tumor cell proliferation, suggesting CALR
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Liposarcomas, a soft tissue sarcoma, exhibit hampered adipogenesis, particularly in the dedifferentiated subtype.
- The specific factors inhibiting adipocyte differentiation in these tumors remain largely unknown.
- Calreticulin (CALR), a calcium-buffering protein, is known to inhibit adipocyte differentiation and was identified as overexpressed in dedifferentiated liposarcoma.
Purpose of the Study:
- To investigate the expression of calreticulin (CALR) at protein and mRNA levels in liposarcoma subtypes.
- To explore the role of CALR and its related microRNA (miR-1257) in the dedifferentiation and progression of liposarcoma.
- To assess the therapeutic potential of down-regulating CALR in dedifferentiated liposarcoma cells.
Main Methods:
- Immunohistochemistry on 45 liposarcoma cases (15 dedifferentiated).
- Western blot and quantitative RT-PCR for CALR expression analysis.
- Fluorescence in situ hybridization for chromosomal abnormalities and miR-1257 expression analysis.
- Small-interfering RNA (siRNA) mediated down-regulation of CALR.
Main Results:
- Calreticulin (CALR) was consistently expressed in dedifferentiated areas and atypical cells of liposarcomas, but not in mature adipocytes.
- Quantitative analyses confirmed CALR overexpression in dedifferentiated liposarcoma.
- Suppression of miR-1257, a CALR-targeting microRNA, was observed in the dedifferentiated subtype.
- Down-regulation of CALR using siRNA induced adipogenesis and reduced proliferation in dedifferentiated liposarcoma cells.
Conclusions:
- Aberrant calreticulin (CALR) expression is implicated in the dedifferentiation and progression of liposarcoma.
- CALR may serve as a potential therapeutic target for managing dedifferentiated liposarcoma.
- Understanding the role of CALR and miR-1257 provides insights into liposarcoma pathogenesis.
Related Concept Videos
02:23Abnormal Proliferation
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...