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.

Highlights

  • Secreted protein acidic and rich in cysteines like 1 (SPARCL1, syn.: Sc1, hevin, MAST9) is a matricellular protein belonging to the SPARC protein family, and SPARC/osteonectin is its closest and most prominent family member [1, 2]

  • Intermediate levels were detected in the coecum, whereas weak levels were detected in the oesophagus, heart and spleen

  • The low levels of RNA expression in the small intestine and kidney did not result in mSparcl1 expression detected at the protein level (Fig 1B)

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Summary

Introduction

Secreted protein acidic and rich in cysteines like 1 (SPARCL1, syn.: Sc1, hevin, MAST9) is a matricellular protein belonging to the SPARC protein family, and SPARC/osteonectin is its closest and most prominent family member [1, 2]. Matricellular proteins are secreted proteins present in the extracellular matrix [3]. They have de-adhesive activity, in contrast to the adhesive extracellular matrix proteins fibronectin, vitronectin, and collagen [3]. Differential SPARCL1 expression in humans and mice. D28 to EN/MS, D34 to MS, J73 to CT, stipendia to AK) of the University Medical Center Erlangen, the German Research Foundation (DFG: FOR 2438, sub-project 2 to EN/MS; TRR 241, sub-project A06 to MS/NBL; KFO 257, sub-project 4 to MS; SFB 796, sub-project B9 to MS), the W. Lutz Stiftung to MS and the Forschungsstiftung Medizin am Universitatsklinikum Erlangen to MS

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