Dataset Information

Inhibition of integrin ?V?6 changes fibril thickness of stromal collagen in experimental carcinomas.

ABSTRACT: 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-?1 and -?3 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 ?V?6 integrin-mediated activation of latent TGF-? 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 ?V?6 integrin-specific monoclonal antibody 3G9 was used to inhibit the ?V?6 integrin activity. RESULTS:Both KAT-4 and Capan-2 cells expressed the ?V?6 integrin but only KAT-4 cells could utilize this integrin to activate latent TGF-? 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-?1 and -?3 reduced collagen fibril thickness in both tumor models. CONCLUSION:Our data demonstrate that the ?V?6-directed activation of latent TGF-? plays a pivotal role in modulating the stromal collagen network in carcinoma, but that the sensitivity to ?V?6 inhibition depends on the simultaneous presence of alternative paths for latent TGF-? activation and the extent of desmoplasia.

SUBMITTER: Olof Olsson P

PROVIDER: S-EPMC6027735 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Inhibition of integrin α<sub>V</sub>β<sub>6</sub> changes fibril thickness of stromal collagen in experimental carcinomas.

Olof Olsson P P Gustafsson Renata R Salnikov Alexei V AV Göthe Maria M Zeller Kathrin S KS Friman Tomas T Baldetorp Bo B Koopman Louise A LA Weinreb Paul H PH Violette Shelia M SM Kalamajski Sebastian S Heldin Nils-Erik NE Rubin Kristofer K

Cell communication and signaling : CCS 20180702 1

<h4>Background</h4>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.<h4>Methods</h4>The potential role of α<sub>V</sub>β<sub>6</sub> integrin-mediated activation of latent TGF-β was studied in cultured KAT-4 a ...[more]

PMID: 29966518

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Dataset Information

Inhibition of integrin ?V?6 changes fibril thickness of stromal collagen in experimental carcinomas.

Publications

Inhibition of integrin α<sub>V</sub>β<sub>6</sub> changes fibril thickness of stromal collagen in experimental carcinomas.

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