Fig. 8 |. Astrocytes recruited to SCLC promote brain tumour growth.

a, Quantification of tumour area after intracranial injection of N2N1G mouse cells with DMSO or tiplaxtinin (n = 6 tumours from 2 experiments) 14 days after injection. b,c, Representative images (b) and quantification (c) of immunofluorescence staining of GFAP in N2N1G allografts treated with DMSO control or tiplaxtinin 7 days after injection. n = 3 independent experiments. Scale bar, 20 μm. d,e, Representative immunofluorescence staining (d) and quantification of Casp3⁺ shCtrl and shReln N2N1G cells (e) growing in the brain of mice. n = 3 independent experiments. Scale bar, 20 μm. f,g, Representative immunofluorescence staining (f) and quantification (g) of Casp3⁺ shCtrl and shReln N2N1G cells overexpressing control vector or SERPINE1 (OE S1) when grown in the brain of mice. n = 3 independent experiments. Scale bar, 20 μm. h,i, Representative H&E images (h) and quantification (i) of tumour size from experiment in (f). Tumours appear dark purple. Scale bar, 2 mm. n = 3 independent experiments. j, Working model: SCLC is a neuroendocrine cancer whose neuronal features are often accentuated during tumour progression, including as SCLC cells reach the brain microenvironment. The neuronal programmes expressed by SCLC cells resemble those of neurons during early brain development and reactive astrocytes associated with SCLC cells in the brain also gain features of astrocytes during brain development. Secretion of the brain development molecule Reelin by SCLC cells recruits reactivated astrocytes to the brain metastasis site. Secretion of factors such as SERPINE1 by astrocytes in turn promotes the survival of SCLC cells.