FIGURE 4. Versican is a TLR2 agonist and metastasis-enhancing factor.

a, Identification of candidate LCM macrophage activators by mass spectrometry. Probability-based Mowse scores (upper) and tryptic peptides corresponding to the indicated proteins (lower). b, LLC were transduced with indicated shRNA lentiviruses. After selection, expression of the indicated proteins was analysed. c, Left: LLC transduced with indicated lentiviruses were injected (2  10⁵ cells) into mice (n = 8). Lung tumour multiplicity was enumerated at 20 days (averages  s.e.m., P < 0.001 by Student's t-test). Right: survival of mice inoculated with LLC transduced with control or Vers shRNAs (n = 9; *P < 0.05; log-rank test for significance). d, Lung and liver tumour multiplicities and incidence of adrenal metastasis 17 days after primary tumour removal (averages  s.e.m., n = 8 and n = 5 for mice injected with control or Vers shRNA-transduced cells, respectively; *P < 0.05 by Student's t-test). e, Upper: non-transfected and human versican (hVers) transfected P29-LLC cells were analysed for versican expression. Lower: hVers non-expressing and expressing P29-LLC cells were injected through the tail vein (n = 7). After 27 days, lung metastatic nodules were enumerated (*P < 0.05 by Student's t-test). f, Left: silver staining of purified 6  His-hVers. Right: BMDM were incubated without or with His-hVers for 20–24 h, and cytokine secretion was measured (averages  s.d., n = 3). g, Lysates of Raw264.7 cells incubated with LCM or SFM for 1 h were immunoprecipitated with versican-specific or control antibody and analysed by immunoblotting with the indicated antibodies.

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