| AVS 64th International Symposium & Exhibition | |
| Biomaterial Interfaces Division | Wednesday Sessions |
| Session BI+NS-WeM |
| Session: | Biomaterials and Nanomaterials Fabrication & In Honor of Dave Castner's 65th Birthday: Multitechnique Bio-Surface Characterization I |
| Presenter: | Blake Bluestein, University of Washington |
| Authors: | B.M. Bluestein, University of Washington F. Morrish, Fred Hutchinson Cancer Research Center D. Hockenbery, Fred Hutchinson Cancer Research Center L.J. Gamble, University of Washington |
| Correspondent: | Click to Email |
Solid tumors are not simply masses of malignant cells but are a structurally complex system, composed of a myriad of cells. The interactions between malignant cells and non-transformed cells form the tumor microenvironment. The tumor microenvironment has been associated with regulating tumor cell growth, metastatic potential, and drug resistance. Here, a combination of techniques including imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS), H&E staining, and second harmonic generation (SHG) microscopy are used to analyze pancreatic biopsies from a mouse model with Myc-dependent inducible pancreatic β-cell neoplasia to relate changes in the composition and distribution of metabolic related molecules with tumor development. Myc, one of the most frequently deregulated oncogenes in human cancers, contributes to tumorigenesis through various mechanisms, including the deregulation of cell proliferation and metabolic alterations.
Pancreatic tissues were harvested and frozen in optimal cutting temperature (OCT) at 6 days post Myc induction and without any Myc induction (control). Cryosections (4 µm thickness) were serially cut, with one used for H&E staining and SHG microscopy, and one for ToF-SIMS analysis. ToF-SIMS data was acquired using an IONTOF TOF.SIMS 5. Regions identified by analysis and principal components analysis (PCA) were cross-referenced against immunohistochemical, H&E, and SHG images to differentiate the tumor areas from the surrounding tissue.
PCA analysis of ToF-SIMS image data separate tumor from surrounding tissue and reveal the differences in chemistries between the two regions. The Myc-induced islet tumors exhibit a signal of C14:0, a likely product of de novo fatty acid synthesis within the islet tumor. Image data shows higher signal regions within the interior of the tumor. These regions exhibit an increased, localized signal of CN-, CNO-, Fe+, and characteristic histidine fragments, C5H8N3+ and C6H5N2O+. SHG images showed that there were no organized structures in these higher signal regions and immunohistochemistry showed no signs of angiogenic processes, confirming that these areas are blood pools resulting from vascular hemorrhaging. Further metabolic analyses showed that when compared to control islets, Myc-induced tumor islets exhibited increased intensities of amino acids and phosphatidylcholine lipids (30:0, 32:1, 32:2), which are known to be related to tumor growth. Tissue surrounding the Myc islet tumors exhibited lower intensities of serine, glycine, and arginine when compared to the tissue surrounding the control islets, which suggests tumor uptake or an increased catabolism induced by the adjacent tumor.