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. 2022 Jul 26;12(10):2454–2473. doi: 10.1158/2159-8290.CD-21-1690

Figure 2.

Figure 2. SCs wrap and align cancer cells. A, Hematoxylin and eosin (H&E) section of a human PDAC specimen with PNI. Scale bar, 200 μm. N, nerve; S, stroma; T, tumor. B, GFAP (green) and cytokeratin (CK; magenta) staining in a section adjacent to A showing cancer cells surrounded by GFAP+ SCs in a nerve. The yellow and orange dotted regions of the nerve are adjacent (A) or distal (D) to the cancer cells. Scale bar, 200 μm. C, Quantification of nerves with an uneven GFAP distribution comparing when cancer is visibly present or absent. D, Quantification of GFAP mean intensity in adjacent and distal regions of nerves (paired t test, P < 0.0001). E, Enlargement of rectangle in A. Scale bar, 50 μm. F, GFAP and CK staining of an adjacent section of E. Scale bar, 50 μm. G, Confocal images corresponding to rectangle 1 in F. Scale bar, 10 μm. H, Confocal images corresponding to rectangle 2 in F. Top image is an xy maximum projection, and the bottom image is an xz image corresponding to the dotted line. Scale bars, 10 μm. I, H&E section of a human PDAC specimen with a nerve (N) and tumor cells (T) in the neighboring stroma (S). Scale bar, 200 μm. J, Enlargement of I. Arrows indicate two cancer cells. Scale bar, 20 μm. K, GFAP and CK staining of a section adjacent to J showing GFAP+ SCs wrapping two cancer cells (arrows). Scale bar, 20 μm. L and M, H&E staining and adjacent GFAP and CK staining of a human PDAC specimen showing GFAP+ SCs around aligned cancer cells. Scale bars, 20 μm. N and O, H&E staining and adjacent GFAP staining of a longitudinal section of a murine sciatic nerve injected with cancer cells. Scale bars, 500 μm. P, Schematic representation of HEI-286 SCs and MiaPaCa-2 cancer cells in a 3D Matrigel invasion assay. The MiaPaCa-2-RFP cancer cells are placed on the surface of a Matrigel chamber in which HEI-286 SCs have grown. Cancer cells invade the gel as a chain of cancer cells surrounded by HEI-286 SC tracks. Q, Maximum projection of confocal images showing a chain of cancer cells lined up within a tubular structure of HEI-286 SCs in Matrigel. Scale bar, 20 μm. R, Single focal planes of confocal images showing MiaPaCa-2 cancer cells and HEI-286 SCs organized into columns. Longitudinal (left) and transverse (right) images correspond to the indicated positions. Scale bars, 20 μm.

SCs wrap and align cancer cells. A, Hematoxylin and eosin (H&E) section of a human PDAC specimen with PNI. Scale bar, 200 μm. N, nerve; S, stroma; T, tumor. B, GFAP (green) and cytokeratin (CK; magenta) staining in a section adjacent to A showing cancer cells surrounded by GFAP+ SCs in a nerve. The yellow and orange dotted regions of the nerve are adjacent (A) or distal (D) to the cancer cells. Scale bar, 200 μm. C, Quantification of nerves with an uneven GFAP distribution comparing when cancer is visibly present or absent. D, Quantification of GFAP mean intensity in adjacent and distal regions of nerves (paired t test, P < 0.0001). E, Enlargement of rectangle in A. Scale bar, 50 μm. F, GFAP and CK staining of an adjacent section of E. Scale bar, 50 μm. G, Confocal images corresponding to rectangle 1 in F. Scale bar, 10 μm. H, Confocal images corresponding to rectangle 2 in F. Top image is an xy maximum projection, and the bottom image is an xz image corresponding to the dotted line. Scale bars, 10 μm. I, H&E section of a human PDAC specimen with a nerve (N) and tumor cells (T) in the neighboring stroma (S). Scale bar, 200 μm. J, Enlargement of I. Arrows indicate two cancer cells. Scale bar, 20 μm. K, GFAP and CK staining of a section adjacent to J showing GFAP+ SCs wrapping two cancer cells (arrows). Scale bar, 20 μm. L and M, H&E staining and adjacent GFAP and CK staining of a human PDAC specimen showing GFAP+ SCs around aligned cancer cells. Scale bars, 20 μm. N and O, H&E staining and adjacent GFAP staining of a longitudinal section of a murine sciatic nerve injected with cancer cells. Scale bars, 500 μm. P, Schematic representation of HEI-286 SCs and MiaPaCa-2 cancer cells in a 3D Matrigel invasion assay. The MiaPaCa-2-RFP cancer cells are placed on the surface of a Matrigel chamber in which HEI-286 SCs have grown. Cancer cells invade the gel as a chain of cancer cells surrounded by HEI-286 SC tracks. Q, Maximum projection of confocal images showing a chain of cancer cells lined up within a tubular structure of HEI-286 SCs in Matrigel. Scale bar, 20 μm. R, Single focal planes of confocal images showing MiaPaCa-2 cancer cells and HEI-286 SCs organized into columns. Longitudinal (left) and transverse (right) images correspond to the indicated positions. Scale bars, 20 μm.