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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
SPARC is expressed in human uveal melanoma and its abrogation reduces tumor cell proliferation
Shawn C Maloney1, Jean-Claude Marshall, Emilia Antecka
1The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, QC, H3A 2B4, Canada. shawn.maloney@mail.mcgill.ca
Background:
Secreted protein acidic and rich in cysteine (SPARC) has been shown to play an integral role in the progression of numerous malignancies. The aim of this study was to investigate the expression of SPARC in uveal melanoma (UM).
Materials And Methods:
SPARC expression was assessed in UM cell lines using RT-PCR and immunocytochemistry. Small interfering RNA directed against SPARC was used to transfect each of the cell lines, which were subsequently run in proliferation assays. SPARC expression was further investigated in 19 cases of human UM and 11 primary and 8 metastatic tumors from a rabbit xenograft model.
Results:
The cell lines transfected with SPARC siRNA showed a significant decrease in proliferation compared to controls. All cases of human uveal melanoma demonstrated positive staining for SPARC as did all primary and metastatic tumors from the xenograft model.
Conclusion:
SPARC may represent a novel target to inhibit growth of UM.
Insights
Secreted protein acidic and rich in cysteine (SPARC) is highly expressed in uveal melanoma (UM). Inhibiting SPARC significantly reduced UM cell proliferation, suggesting it is a potential therapeutic target for this eye cancer.
Area of Science:
- Oncology
- Ophthalmology
- Molecular Biology
Background:
- Secreted protein acidic and rich in cysteine (SPARC) is implicated in various cancer progressions.
- Uveal melanoma (UM) is a primary intraocular malignancy.
- The role of SPARC in UM pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the expression levels of SPARC in uveal melanoma.
- To determine the functional role of SPARC in UM cell proliferation.
- To evaluate SPARC as a potential therapeutic target for UM.
Main Methods:
- SPARC expression was analyzed in UM cell lines and human UM tissues using RT-PCR and immunocytochemistry.
- UM cell lines were transfected with SPARC-targeting small interfering RNA (siRNA).
- Proliferation assays were performed on transfected cell lines and in a rabbit xenograft model.
Main Results:
- SPARC siRNA transfection led to a significant reduction in UM cell proliferation compared to control groups.
- All examined human UM cases showed positive SPARC staining.
- SPARC was also expressed in primary and metastatic tumors from a rabbit xenograft model.
Conclusions:
- SPARC is highly expressed in uveal melanoma.
- SPARC plays a role in promoting UM cell growth.
- Targeting SPARC may offer a novel therapeutic strategy for inhibiting UM progression.
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