Extended Data Fig. 7: EVs promote axonogenesis and PDAC progression. | Nature Cell Biology

Extended Data Fig. 7: EVs promote axonogenesis and PDAC progression.

From: Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer via extracellular vesicle transfer of RNA

Extended Data Fig. 7

a, The evidence of Alkbh5 KO, or Alkbh5 and Rab27a double KO in KPC cells. b, Alkbh5 KO had no effect on EV production and Rab27a KO significantly suppressed the EV production in KPC cells (n = 5 independent experiments). c–e, Rab27a KO significantly suppressed Alkbh5 KO-induced tumor nerve innervation (c, β3-tubulin+) including sympathetic nerve (d, TH+) and sensory nerve (e, Trpv1+) innervation in mouse allograft tumors (n = 5 mice). f, Rab27a KO partially suppressed Alkbh5 KO-induced growth of mouse allograft tumors (n = 5 mice). g, Rab27a KO partially prolonged Alkbh5 KO-reduced survival time of mice bearing allograft tumors (n = 8 mice). h, Experimental scheme of EV treatment in Fig. 4d. i and j, Effect of EVs produced by wide-type KPC cells or Alkbh5-KO KPC cells on sympathetic nerve (i, TH+) and sensory nerve (j, Trpv1+) innervation in PDAC tumor tissue of KPC mice (n = 5 KPC mice). Left panel shows immunofluorescence in tumor tissue and right panel shows quantitative statistics. k and l, Effect of EVs produced by wide-type KPC cells or Alkbh5-KO KPC cells on the axonogenesis of DRG neurons (k) and sympathetic neurons (l) from celiac ganglia (n = 5 independent experiments). m, Axonogenesis examination by coculture of Alkbh5-KO or Alkbh5- and Rab27a-double KO KPC cells (left) and DRG (right) in confocal dish at same plane. n, EVs derived from Alkbh5-KO KPC cells treatment had no obvious effects on Alkbh5-KO KPC cell proliferation (left, n = 4 independent experiments), migration (middle, n = 5 independent experiments) and invasion ability (right, n = 5 independent experiments). o, Rab27a KO had no obvious effects on Alkbh5-KO KPC cell proliferation (left, n = 4 independent experiments), migration (middle, n = 5 independent experiments) and invasion ability (right, n = 5 independent experiments). Scale bars, 200 μm (c–e, i, j), 50 μm (k), 20 μm (l). Bar chart data are the means ± s.e.m., with P by two-tailed Student’s t-test in b–f and i–o, or by log-rank test in g.

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