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Updated: Jul 1, 2026

Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Expression of insulin-like growth factor pathway proteins in rhabdomyosarcoma: IGF-2 expression is associated with
Shalini Makawita1, Michael Ho, Adam D Durbin
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Abstract:
Recent studies have shown a significant involvement of insulin-like growth factor (IGF) signaling components in the pathogenesis of rhabdomyosarcoma (RMS). Furthermore, there has been some evidence to indicate that differential expression of IGF pathway genes can distinguish RMS subtypes. The present study utilized immunohistochemistry to determine the expression patterns of IGF1, IGF2, IGF binding protein 2 (IGFBP2), IGF receptor 1 (IGF1R), and IGF receptor 2 (IGF2R) in 24 embryonal RMS (ERMS) and 8 alveolar RMS (ARMS). A majority of tumors were positive for IGF2, IGFBP2, IGF1R, and IGF2R and negative for IGF1 expression. However, only IGF2 showed a significant difference in expression between the ERMS and ARMS subtypes, with higher levels of expression in ERMS (P = 0.0003). Within the ARMS subtype, IGF2 positivity was limited to PAX/FKHR translocation-negative tumors. The staining pattern for all 5 proteins was diffuse cytoplasmic in the majority of tumors. Analysis of RMS cell lines by real-time reverse transcriptase-polymerase chain reaction for IGF2 expression revealed significantly higher mean expression levels in ERMS and translocation-negative ARMS cell lines when compared to translocation-positive ARMS cell lines (P = 0.0027). Stable introduction of PAX3/FKHR into an ERMS cell line also demonstrated a significant reduction in IGF2 expression. The results of this study show that expression of the IGF2 ligand is associated with translocation-negative tumors and may serve as a diagnostic aid in distinguishing RMS subtypes. Furthermore, the in vitro results are supportive of a role for the PAX3/FKHR fusion gene in the inhibition of IGF2 expression.
Insights
Insulin-like growth factor 2 (IGF2) expression differs between rhabdomyosarcoma (RMS) subtypes. Higher IGF2 levels in embryonal RMS and translocation-negative alveolar RMS suggest it may aid in distinguishing RMS subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Insulin-like growth factor (IGF) signaling is implicated in rhabdomyosarcoma (RMS) pathogenesis.
- Differential gene expression within the IGF pathway may distinguish RMS subtypes.
Purpose of the Study:
- To investigate the expression patterns of IGF1, IGF2, IGFBP2, IGF1R, and IGF2R in ERMS and ARMS.
- To determine if IGF pathway gene expression can differentiate between RMS subtypes.
Main Methods:
- Immunohistochemistry was used to analyze protein expression in 32 RMS tumors (24 ERMS, 8 ARMS).
- Real-time RT-PCR was performed on RMS cell lines to assess IGF2 mRNA levels.
- PAX3/FKHR fusion gene introduction into an ERMS cell line was utilized for in vitro analysis.
Main Results:
- IGF2, IGFBP2, IGF1R, and IGF2R were frequently expressed, while IGF1 was largely negative.
- IGF2 expression was significantly higher in ERMS compared to ARMS (P = 0.0003).
- In ARMS, IGF2 positivity was restricted to PAX/FKHR translocation-negative tumors. In vitro studies confirmed IGF2 downregulation by PAX3/FKHR.
Conclusions:
- IGF2 ligand expression is associated with translocation-negative RMS and may serve as a diagnostic marker for distinguishing subtypes.
- The PAX3/FKHR fusion gene appears to inhibit IGF2 expression, as supported by in vitro findings.
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