UZH-Logo

Maintenance Infos

Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects


Stevenson, J L; Varki, A; Borsig, L (2007). Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects. Thrombosis Research, 120(Suppl):S107-S111.

Abstract

Heparin and low molecular weight heparin (LMWH) are widely used for treatment of cancer patients with thrombosis, a common complication of malignant disease. Several recent prospective clinical studies indicate that heparin might improve outcomes of human cancer. Meanwhile, experimental evidence from mouse models consistently demonstrates that heparin efficiently inhibits metastasis. We have previously shown that P- and L-selectin play independent roles in supporting the initial stages of hematogeneous metastasis. Heparin is a known potent inhibitor of such selectin-mediated interactions. Here we provide evidence that the absence of both P- and L-selectin (PL -/- mice) dramatically improved survival in an experimental metastasis model. The use of clinically acceptable amounts of heparin did not further aff5ct metastasis rates in such mice. However, a non-anticoagulant derivative of heparin with P- and L-selectin inhibitory properties reduced metastasis to similar levels as observed in PL -/- mice. The virtual elimination of metastasis by a single treatment with a modified heparin without anticoagulant activity strongly suggests that heparin primarily reduces metastatic disease by inhibiting P- and L-selectin interactions. However, such heparins could have further effects at higher doses.

Abstract

Heparin and low molecular weight heparin (LMWH) are widely used for treatment of cancer patients with thrombosis, a common complication of malignant disease. Several recent prospective clinical studies indicate that heparin might improve outcomes of human cancer. Meanwhile, experimental evidence from mouse models consistently demonstrates that heparin efficiently inhibits metastasis. We have previously shown that P- and L-selectin play independent roles in supporting the initial stages of hematogeneous metastasis. Heparin is a known potent inhibitor of such selectin-mediated interactions. Here we provide evidence that the absence of both P- and L-selectin (PL -/- mice) dramatically improved survival in an experimental metastasis model. The use of clinically acceptable amounts of heparin did not further aff5ct metastasis rates in such mice. However, a non-anticoagulant derivative of heparin with P- and L-selectin inhibitory properties reduced metastasis to similar levels as observed in PL -/- mice. The virtual elimination of metastasis by a single treatment with a modified heparin without anticoagulant activity strongly suggests that heparin primarily reduces metastatic disease by inhibiting P- and L-selectin interactions. However, such heparins could have further effects at higher doses.

Citations

54 citations in Web of Science®
68 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 22 Mar 2009
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2007
Deposited On:22 Mar 2009 19:15
Last Modified:05 Apr 2016 13:01
Publisher:Elsevier
ISSN:0049-3848
Additional Information:Erratum in: Thromb Res. 2008;123(1):187-90.
Publisher DOI:https://doi.org/10.1016/S0049-3848(07)70138-X
PubMed ID:18023703

Download

[img]
Filetype: PDF - Registered users only
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations