Unfractionated Heparin Selectively Modulates the Expression of CXCL8, CCL2 and CCL5 in Endometrial Carcinoma Cells

未分级肝素选择性调节子宫内膜癌细胞中 CXCL8、CCL2 和 CCL5 的表达

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作者:Anne Doster, Ulrike Schwarzig, Marek Zygmunt, Joachim Rom, Florian Schütz, Herbert Fluhr

Aim

This in vitro study analyzed the impact of heparins on expression of chemokines in human endometrial adenocarcinoma cell lines. Materials and

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.

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.

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