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Tumor-suppressor function of SPARC-like protein 1/Hevin in pancreatic cancer
Irene Esposito1, Hany Kayed, Shereen Keleg
1Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Abstract:
SPARC-like protein 1 (SPARCL1), a member of the SPARC family, is downregulated in various tumors. In the present study, the expression and localization of SPARCL1 were analyzed in a wide range of nontumorous and neoplastic pancreatic tissues by quantitative reverse transcription-polymerase chain reaction, laser capture microdissection, microarray analysis, and immunohistochemistry. For functional analysis, proliferation and invasion assays were used in cultured pancreatic cancer cells. Pancreatic ductal adenocarcinoma (PDAC) and other pancreatic neoplasms exhibited increased SPARCL1 mRNA levels compared to those of the normal pancreas. SPARCL1 mRNA levels were low to absent in microdissected and cultured pancreatic cancer cells, and promoter demethylation increased SPARCL1 levels only slightly in three of eight cell lines. SPARCL1 was observed in small capillaries in areas of inflammation/tumor growth and in some islet cells. In PDAC, 15.4% of vessels were SPARCL1-positive. In contrast, the percentage of SPARCL1-positive vessels was higher in chronic pancreatitis and benign and borderline pancreatic tumors. Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and exerted moderate growth-inhibitory effects. In conclusion, SPARCL1 expression in pancreatic tissues is highly correlated with level of vascularity. Its anti-invasive effects and reduced expression in metastasis indicate tumor-suppressor function.
Insights
SPARC-like protein 1 (SPARCL1) shows varied expression in pancreatic tissues, with reduced levels in cancer cells but increased presence in tumor-associated vasculature. SPARCL1 inhibits invasion, suggesting a tumor-suppressor role.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- SPARC-like protein 1 (SPARCL1), a member of the SPARC family, is known to be downregulated in various tumors.
- Understanding SPARCL1's role in pancreatic cancer is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To analyze the expression and localization of SPARCL1 in nontumorous and neoplastic pancreatic tissues.
- To investigate the functional role of SPARCL1 in pancreatic cancer cell proliferation and invasion.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
- Laser capture microdissection (LCM)
- Microarray analysis
- Immunohistochemistry (IHC)
- In vitro proliferation and invasion assays
Main Results:
- Pancreatic ductal adenocarcinoma (PDAC) and other neoplasms showed increased SPARCL1 mRNA levels compared to normal pancreas.
- SPARCL1 mRNA levels were low in microdissected and cultured pancreatic cancer cells.
- SPARCL1 was detected in capillaries within inflammatory/tumor areas and islet cells, with higher vessel positivity in benign/borderline tumors and chronic pancreatitis than in PDAC.
- Recombinant SPARCL1 inhibited pancreatic cancer cell invasion and moderately inhibited growth.
Conclusions:
- SPARCL1 expression in pancreatic tissues correlates with vascularity.
- SPARCL1 exhibits anti-invasive effects and reduced expression in metastasis, indicating a tumor-suppressor function.
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