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Sebastian Kalamajski

Assistant researcher

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Inhibition of integrin αvβ6 changes fibril thickness of stromal collagen in experimental carcinomas


  • P. Olof Olsson
  • Renata Gustafsson
  • Alexei V. Salnikov
  • Maria Göthe
  • Kathrin S. Zeller
  • Tomas Friman
  • Bo Baldetorp
  • Louise A. Koopman
  • Paul H. Weinreb
  • Shelia M. Violette
  • Sebastian Kalamajski
  • Nils Erik Heldin
  • Kristofer Rubin

Summary, in English

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.


  • Department of Experimental Medical Science
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year





Cell Communication and Signaling





Document type

Journal article


BioMed Central (BMC)


  • Cancer and Oncology




  • ISSN: 1478-811X