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Inhibition of integ...
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Olof Olsson, P.Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
(författare)
Inhibition of integrin αvβ6 changes fibril thickness of stromal collagen in experimental carcinomas
- Artikel/kapitelEngelska2018
Förlag, utgivningsår, omfång ...
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2018-07-02
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Springer Science and Business Media LLC,2018
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:ecc1464b-61c1-4cdf-875f-15827de3faca
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https://lup.lub.lu.se/record/ecc1464b-61c1-4cdf-875f-15827de3facaURI
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https://doi.org/10.1186/s12964-018-0249-7DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Background: Chemotherapeutic efficacy can be improved by targeting the structure and function of the extracellular matrix (ECM) in the carcinomal stroma. This can be accomplished by e.g. inhibiting TGF-β1 and -β3 or treating with Imatinib, which results in scarcer collagen fibril structure in xenografted human KAT-4/HT29 (KAT-4) colon adenocarcinoma. Methods: The potential role of αVβ6 integrin-mediated activation of latent TGF-β was studied in cultured KAT-4 and Capan-2 human ductal pancreatic carcinoma cells as well as in xenograft carcinoma generated by these cells. The monoclonal αVβ6 integrin-specific monoclonal antibody 3G9 was used to inhibit the αVβ6 integrin activity. Results: Both KAT-4 and Capan-2 cells expressed the αVβ6 integrin but only KAT-4 cells could utilize this integrin to activate latent TGF-β in vitro. Only when Capan-2 cells were co-cultured with human F99 fibroblasts was the integrin activation mechanism triggered, suggesting a more complex, fibroblast-dependent, activation pathway. In nude mice, a 10-day treatment with 3G9 reduced collagen fibril thickness and interstitial fluid pressure in KAT-4 but not in the more desmoplastic Capan-2 tumors that, to achieve a similar effect, required a prolonged 3G9 treatment. In contrast, a 10-day direct inhibition of TGF-β1 and -β3 reduced collagen fibril thickness in both tumor models. Conclusion: Our data demonstrate that the αVβ6-directed activation of latent TGF-β plays a pivotal role in modulating the stromal collagen network in carcinoma, but that the sensitivity to αVβ6 inhibition depends on the simultaneous presence of alternative paths for latent TGF-β activation and the extent of desmoplasia.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Gustafsson, RenataLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)medk-rme
(författare)
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Salnikov, Alexei V.Skåne University Hospital(Swepub:lu)med-axs
(författare)
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Göthe, MariaUppsala University
(författare)
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Zeller, Kathrin S.Uppsala University(Swepub:lu)immu-kaz
(författare)
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Friman, TomasUppsala University
(författare)
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Baldetorp, BoLund University,Lunds universitet,Skåne University Hospital(Swepub:lu)onk-bba
(författare)
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Koopman, Louise A.Biogen, Inc.
(författare)
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Weinreb, Paul H.Biogen, Inc.
(författare)
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Violette, Shelia M.Biogen, Inc.
(författare)
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Kalamajski, SebastianUppsala University(Swepub:lu)se8335ka
(författare)
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Heldin, Nils ErikUppsala University
(författare)
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Rubin, KristoferUppsala University(Swepub:lu)med-krn
(författare)
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Institutionen för experimentell medicinsk vetenskapMedicinska fakulteten
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cell Communication and Signaling: Springer Science and Business Media LLC16:11478-811X
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Olof Olsson, P.
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Gustafsson, Rena ...
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Salnikov, Alexei ...
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Göthe, Maria
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Zeller, Kathrin ...
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Friman, Tomas
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Baldetorp, Bo
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Koopman, Louise ...
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Weinreb, Paul H.
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Violette, Shelia ...
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Kalamajski, Seba ...
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Heldin, Nils Eri ...
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Rubin, Kristofer
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