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Open Access Research article

SPARC expression in CML is associated to imatinib treatment and to inhibition of leukemia cell proliferation

Cesarina Giallongo1, Piera La Cava1, Daniele Tibullo1*, Ignazio Barbagallo2, Nunziatina Parrinello1, Alessandra Cupri1, Fabio Stagno1, Carla Consoli1, Annalisa Chiarenza1, Giuseppe A Palumbo1 and Francesco Di Raimondo1

Author affiliations

1 Department of Clinical and Molecular Biomedicine, University of Catania, Ospedale Ferrarotto, V. Citelli 6, 95124, Catania, Italy

2 Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy

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Citation and License

BMC Cancer 2013, 13:60  doi:10.1186/1471-2407-13-60

Published: 5 February 2013

Abstract

Background

SPARC is a matricellular glycoprotein with growth-inhibitory and antiangiogenic activity in some cell types. The study of this protein in hematopoietic malignancies led to conflicting reports about its role as a tumor suppressor or promoter, depending on its different functions in the tumor microenvironment. In this study we investigated the variations in SPARC production by peripheral blood cells from chronic myeloid leukemia (CML) patients at diagnosis and after treatment and we identified the subpopulation of cells that are the prevalent source of SPARC.

Methods

We evaluated SPARC expression using real-time PCR and western blotting. SPARC serum levels were detected by ELISA assay. Finally we analyzed the interaction between exogenous SPARC and imatinib (IM), in vitro, using ATP-lite and cell cycle analysis.

Results

Our study shows that the CML cells of patients at diagnosis have a low mRNA and protein expression of SPARC. Low serum levels of this protein are also recorded in CML patients at diagnosis. However, after IM treatment we observed an increase of SPARC mRNA, protein, and serum level in the peripheral blood of these patients that had already started at 3 months and was maintained for at least the 18 months of observation. This SPARC increase was predominantly due to monocyte production. In addition, exogenous SPARC protein reduced the growth of K562 cell line and synergized in vitro with IM by inhibiting cell cycle progression from G1 to S phase.

Conclusion

Our results suggest that low endogenous SPARC expression is a constant feature of BCR/ABL positive cells and that IM treatment induces SPARC overproduction by normal cells. This exogenous SPARC may inhibit CML cell proliferation and may synergize with IM activity against CML.

Keywords:
CML; Imatinib; SPARC; Granulocytes; Monocytes