Tenascin-C expression in the lymph node pre-metastatic niche in muscle-invasive bladder cancer
Menée à l'aide d'échantillons de tissus ganglionnaires prélevés sur 47 patients atteints d'un cancer invasif de la vessie métastatique ou non, cette étude évalue l'association entre le niveau d'expression de la ténascine C dans les ganglions lymphatiques régionaux, la présence de certaines cytokines dans les vésicules extracellulaires issues de la tumeur et le risque de métastases
Background : Markers of stromal activation at future metastatic sites may have prognostic value and may allow clinicians to identify and abolish the pre-metastatic niche to prevent metastasis. In this study, we evaluate tenascin-C as a marker of pre-metastatic niche formation in bladder cancer patient lymph nodes.
Methods : Tenascin-C expression in benign lymph nodes was compared between metastatic (n = 20) and non-metastatic (n = 27) patients with muscle-invasive bladder cancer. Urinary extracellular vesicle (EV) cytokine levels were measured with an antibody array to examine potential correlation with lymph node inflammation. The ability of bladder cancer EVs to activate primary bladder fibroblasts was assessed in vitro.
Results : Lymph node tenascin-C expression was elevated in metastatic patients vs. non-metastatic patients, and high expression was associated with worse survival. Urinary EVs contained four cytokines that were positively correlated with lymph node tenascin-C expression. Bladder cancer EVs induced tenascin-C expression in fibroblasts in an NF-
κB-dependent manner.
Conclusions
:
Tenascin-C expression in regional lymph nodes may be a good predictor of bladder cancer metastasis and an appropriate imaging target. It may be possible to interrupt pre-metastatic niche formation by targeting EV-borne tumour cytokines or by targeting tenascin-C directly.
British Journal of Cancer , article en libre accès, 2021