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  • Gockel, Lukas M.Univ Bonn, Pharmaceut Inst, Pharmaceut & Cell Biol Chem, D-53121 Bonn, Germany. (author)

Inhibition of Tumor-Host Cell Interactions Using Synthetic Heparin Mimetics

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-02-03
  • American Chemical Society (ACS),2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-441086
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-441086URI
  • https://doi.org/10.1021/acsami.0c20744DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Low-molecular-weight heparin (LMWH) is the guideline-based drug for antithrombotic treatment of cancer patients, while its direct antitumor effects are a matter of ongoing debate. Although therapeutically established for decades, LMWH has several drawbacks mainly associated with its origin from animal sources. Aiming to overcome these limitations, a library of synthetic heparin mimetic polymers consisting of homo- and copolymers of sulfonated and carboxylated noncarbohydrate monomers has recently been synthesized via reversible addition-fragmentation chain transfer polymerization. These heparin mimetics were investigated for their capacities to interfere with simulated steps of tumor cell metastasis. Among them, homo- and copolymers from sodium 4-styrenesulfonate (poly(SSS)) with acrylic acid (poly(SSS-co-AA)) with an MW between 5 and 50 kDa efficiently attenuated cancer cell-induced coagulation and thus platelet activation and degranulation similar to or even better than LMWH. Furthermore, independent of anticoagulant activities, these polymers affected other metastasis-relevant targets with impressive affinities. Hence, they blocked heparanase enzymatic activity outmatching commercial heparins or a glycosidic drug candidate. Furthermore, these polymers bind P-selectin and the integrin VLA-4 similar to or even better than heparin, indicated by a biosensor approach and thus efficiently blocked melanoma cell binding to endothelium under blood flow conditions. This is the first report on the prospects of synthetic heparin mimetics as promising nontoxic compounds in oncology to potentially substitute heparin as an anticoagulant and to better understand its role as an antimetastatic drug.

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  • Heyes, MartinUniv Bonn, Pharmaceut Inst, Pharmaceut & Cell Biol Chem, D-53121 Bonn, Germany. (author)
  • Li, HonglianUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)honli111 (author)
  • Al Nahain, AbdullahUniv Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia.;Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld 4072, Australia. (author)
  • Gorzelanny, ChristianUniv Med Ctr Hamburg Eppendorf, Expt Dermatol, Dept Dermatol & Venereol, D-20246 Hamburg, Germany. (author)
  • Schlesinger, MartinUniv Bonn, Pharmaceut Inst, Pharmaceut & Cell Biol Chem, D-53121 Bonn, Germany. (author)
  • Holdenrieder, StefanTech Univ Munich, Lab Med, German Heart Ctr, D-80636 Munich, Germany. (author)
  • Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)jinpili (author)
  • Ferro, VitoUniv Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia.;Univ Queensland, Australian Infect Dis Res Ctr, Brisbane, Qld 4072, Australia. (author)
  • Bendas, GerdUniv Bonn, Pharmaceut Inst, Pharmaceut & Cell Biol Chem, D-53121 Bonn, Germany. (author)
  • Univ Bonn, Pharmaceut Inst, Pharmaceut & Cell Biol Chem, D-53121 Bonn, Germany.Institutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)

Related titles

  • In:ACS Applied Materials and Interfaces: American Chemical Society (ACS)13:6, s. 7080-70931944-82441944-8252

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