Figure 1.

Asbestos and CNT Fiber-Induced Pleural Lesions Exhibit Common Length-Dependent Molecular Changes

(A) Left: transmission electron microscopy (TEM) images of the fiber panel; scale bars, 1 μm. Right: hematoxylin and eosin (H&E) images of the chest wall of mice at 1 and 12 weeks post-injection of the fiber panel (SFA, SNT, LFA, or LNT) compared to VC. Scale bars, 20 μm.

(B) Cell types within the lesion were quantified (700–1,000 cells per cell marker, per treatment group; n = 4 per group) according to immunostaining (Figure S2) at 1 week and 12 weeks.

(C) Gene expression pattern in control and fiber-exposed animals at 12 weeks post-injection. The heatmap displays the expression level of mRNAs extracted from the diaphragms of animals exposed to SFA, SNT, LFA, or LNT and VC (n = 4 per group). Legend bar shows the color code for the normalized intensity values.

(D and E) Antibody array-based kinome profiling. (D) Common pattern of kinase activation induced by exposure to LFA and LNT at 1 and 12 weeks relative to VC (100%). (E) Activation of signaling pathways in human mesothelioma tissue from five patients is shown relative to kinase activity in normal primary mesothelial cells (control).

(F) Human mesothelioma tissue was analyzed for phospho-STAT3 (Y705), phospho-ERK1/2 (T202/204), phospho-Akt (S473), and phospho-Src (Y418) by western blotting and compared to normal primary mesothelial cells (control). Representative data from six patients are shown.

(G) Immunostaining of signaling proteins in paraffin-embedded sections of human mesothelioma tissue in relation to cancerous (M) and non-cancerous (L, lymphocytes; F, fibroblasts) cells. Representative data from three patients are shown. Scale bars, 100 μm.

See also Figures S1–S3 and Tables S1–S3.