Secreted Protein Acidic and Rich in Cysteine (SPARC) and Chemokine’s mRNA expression in Endometrial Cancer versus Normal Endometrium: A Possible Pattern of Haematogenous and Lymphovascular Metastases

Abstract

Objectives: Secreted Protein Acidic and Rich in Cysteine (SPARC) is a multifunctional glycoprotein, participating in tissue remodeling, morphogenesis and bone mineralization. Furthermore, SPARC controls important mechanisms involved in cancer progression, including angiogenesis regulation. However, in some studies SPARC was found to show tumor suppression while in other a protumorigenic and prometastatic action. In tumor microenvironment some chemokines and their receptors, thanks to their ability to modulate cancer cells migration and proliferation, are involved in the angiogenetic and metastatic process. In this study we compared, in human endometrial cancer tissue (EC) vs normal endometrium counterpart (NE), SPARC with CXCL12, CXCL11, CXCL8, and CXCR7 mRNA expression. Material and Methods: Fresh specimens from 15 patients with EC and corresponding NE were stored at –80°. One mcg of mRNA was reverse-transcribed in cDNA. A Real-Time PCR determined relative cDNA levels of targeted gene mRNA. Results: In EC vs NE, we observed down-regulation of SPARC mRNA in 91% (P<.05), down regulation of CXCL12 mRNA in 91% (P<.001), and down-regulation of CXCR7 mRNA in 91% (P<.001). In EC, SPARC mRNA down-regulation was directly related in 100% of samples to CXCL12 and CXCR7 (P<.001) and in 73% of samples to VEGF (P<.03). Conclusion: In endometrial cancer, under expression of SPARC is directly related to CXCL12 and CXCR7 and this result might be consistent with a SPARC function on tumor progression and invasion mediated by CXCL12 and CXCR7 on blood and lymphatic spread, respectively.