Fig. 4 |. De novo transdifferentiated cancer-associated adrenergic nerves support tumour growth.

a, BALB/c (nu/nu) mice were chemically sympathectomized by intraperitoneal injection of 6-OHDA and then injected orthotopically with p53^null PCI-13 cells. Tumour volume was monitored for 3 weeks. b, Illustrative immunohistochemical analysis for TH⁺ neural fibres in tongues from mice with or without tumours and with or without sympathectomy. Blue arrowheads, pre-existing TH⁺ perivascular neural fibres; red arrowheads, non-perivascular TH⁺ fibres that emerged after tumour formation (cancer-associated nerves); data independently replicated in 32 mice. c, Perivascular and cancer-associated TH⁺ area (n = 8 mice per condition). d, Noradrenaline levels in tumour-bearing tongue (ipsilateral to tumour injection site), adjacent normal tongue (contralateral to tumour injection site), and normal tongue controls (n = 3). e, BALB/c (nu/nu) mice were orthotopically xenografted with p53^null PCI-13 cells to the denervated or sham-operated tongue. f, Quantification of TH⁺ nerve fibres in mice from e (n = 8 mice per condition). g, h, In vivo p53^null PCI-13 tumour growth after lingual denervation (blue, n = 12) compared with sham surgery controls (n = 10, g), or chemical sympathectomy (red, n = 12) compared with vehicle controls (n = 11, h). Bar graphs and tumour growth curves represent mean ± s.e.m. Unpaired two-tailed t-test (g, h) or one-way ANOVA with Tukey multiple comparisons (c, d, f).