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Species-, organ- and cell-type-dependent expression of SPARCL1 in human and mouse tissues
Anika Klingler1, Daniela Regensburger1, Clara Tenkerian1
1Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Translational Research Center, Erlangen, Germany.
Abstract:
SPARCL1 is a matricellular protein with anti-adhesive, anti-proliferative and anti-tumorigenic functions and is frequently downregulated in tumors such as colorectal carcinoma or non-small cell lung cancer. Studies have identified SPARCL1 as an angiocrine tumor suppressor secreted by tumor vessel endothelial cells, thereby exerting inhibitory activity on angiogenesis and tumor growth, in colorectal carcinoma. It is unknown whether SPARCL1 may exert these homeostatic functions in all organs and in other species. Therefore, SPARCL1 expression was comparatively analysed between humans and mice in a systematic manner. Murine Sparcl1 (mSparcl1) is most strongly expressed in the lung; expressed at an intermediate level in most organs, including the large intestine; and absent in the liver. In human tissues, SPARCL1 (hSPARCL1) was detected in all organs, with the strongest expression in the stomach, large intestine and lung, mostly consistent with the murine expression pattern. A striking difference between human and murine tissues was the absence of mSparcl1 expression in murine livers, while human livers showed moderate expression. Furthermore, mSparcl1 was predominantly associated with mural cells, whereas hSPARCL1 was detected in both mural and endothelial cells. Human SPARCL1 expression was downregulated in different carcinomas, including lung and colon cancers. In conclusion, this study revealed species-, organ- and cell-type-dependent expression of SPARCL1, suggesting that its function may not be similar between humans and mice.
Insights
SPARCL1 protein, known for tumor suppression, shows varied expression in human and mouse tissues. Its presence differs significantly in livers and cell associations between species, impacting potential functional similarities.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- SPARCL1 is a matricellular protein with anti-tumorigenic functions.
- It acts as an angiocrine tumor suppressor, inhibiting angiogenesis and tumor growth.
- Its expression and function across different species and organs remain largely uncharacterized.
Purpose of the Study:
- To systematically compare SPARCL1 expression between humans and mice.
- To investigate species-, organ-, and cell-type-specific expression patterns of SPARCL1.
- To understand potential differences in SPARCL1 function between humans and mice.
Main Methods:
- Comparative analysis of SPARCL1 expression in human and murine tissues.
- Utilized immunohistochemistry or similar techniques to detect SPARCL1 localization.
- Correlated SPARCL1 expression with specific cell types (endothelial, mural) and organs.
Main Results:
- Murine Sparcl1 (mSparcl1) is highly expressed in lungs, intermediate in the large intestine, and absent in the liver.
- Human SPARCL1 (hSPARCL1) is detected in all organs, notably in the stomach, large intestine, and lung.
- A key difference was the absence of mSparcl1 in murine livers versus moderate hSPARCL1 expression in human livers.
- mSparcl1 associated with mural cells, while hSPARCL1 was found in both mural and endothelial cells.
- Human SPARCL1 expression was downregulated in lung and colon carcinomas.
Conclusions:
- SPARCL1 exhibits species-, organ-, and cell-type-dependent expression patterns.
- Significant differences in SPARCL1 expression, particularly in the liver, exist between humans and mice.
- These variations suggest that SPARCL1's homeostatic and anti-tumorigenic functions may not be conserved between humans and mice.
