Extended Data Fig. 5: Nerve fibers in the SCLC microenvironment.
From: Functional synapses between neurons and small cell lung cancer
a-h) Confocal images of lung cryostat sections of RP mice. L: lumen of the airways. E: airway epithelium. a) Intraepithelial VGluT1+ nerve terminals (arrowheads) branch between the CGRP+ PNECs. b) Intraepithelial P2X3+ nerve terminals (arrowheads) protruding between the CGRP+ (green) neuroendocrine cells of a NEB. c) GAP43+ nerve fibers (arrows) branch and protrude (arrowheads) between the CGRP+ PNECs. d) A GAP43+ nerve fiber (arrow) branches (arrowheads) between the CGRP + SCLC cells (green). CGRP+ nerve fibers (open arrows) are seen close to the base of the tumor. e) Subepithelial SYP+ and CGRP+ nerve terminals (arrows) innervate a NEB. Remarkable is that the subepithelial area adjacent to a large tumor appears devoid of nerve fibers. f) Small tumor (ST) from an RPC mouse, with no visible innervation from VGluT1+ fibers. Varicose CGRP+ fibers are visible below the tumor (open arrowheads). g) Large tumor (LT) surrounded by varicose CGRP+ and substance P+ (SP) nerve fibers. h) SYP+ (arrows) and CGRP+ (open arrows) nerve fibers can be seen in the epithelium at the base of a small tumor (ST). i) Electron micrographs showing a cancer cell surrounded by long axon-like fibers near the periphery of a tumor in the lung of an RP mouse. j, k) Magnifications showing the presence of enlarged structures along identified fibers (yellow pseudocolor) containing multiple vesicles and mitochondria (M) near the cancer cell (red pseudocolor). l-p) DAB staining of biopsies from three SCLC patients. All sections are counterstained with hemalum. l) NF-H-positive nerve fibers near an intratumoral vessel in the biopsy from the first patient. m, n) NF-H-positive nerve fibers at the borders of a SYP-positive tumor in a biopsy from the second patient. o, p) NF-H-positive nerve fibers at the borders of a SYP-positive tumor in a biopsy from a third patient.
