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Unfractionated Heparin Selectively Modulates the Expression of CXCL8, CCL2 and CCL5 in Endometrial Carcinoma Cells
Anne Doster1, Ulrike Schwarzig2, Marek Zygmunt2
1Department of Obstetrics and Gynecology, University Hospital of Heidelberg, Heidelberg, Germany.
Background/Aim:
This in vitro study analyzed the impact of heparins on expression of chemokines in human endometrial adenocarcinoma cell lines.
Materials And Methods:
Cell lines were incubated with unfractionated heparin (UFH), low molecular weight heparins (LMWH) and fondparinux under hypoxic and normoxic conditions. Chemokine (C-X-C motif) ligand 8 (CXCL8), CC-chemokine ligand 2 (CCL2) and CCL5 were detected by enzyme-linked immunosorbent assays and real-time reverse transcriptase-polymerase chain reaction and cell viability by fluorometric assay.
Results:
Different adenocarcinoma cell lines had distinct patterns of chemokine expression. UFH attenuated the secretion of CXCL8 and CCL2, and enhanced that of CCL5. The observed effects of heparin were in addition to the anti-coagulatory properties of heparin and dependent on molecular size and charge.
Conclusion:
UFH has selective modulating effects on the secretion of CXCL8, CCL2 and CCL5 in different endometrial adenocarcinoma cell lines. Molecular size and charge are relevant for these observed effects. By influencing the expression of these inflammatory mediators and thereby affecting the tumour microenvironment, heparins and related agents might play an essential role in the development of new therapeutic strategies.
