| AVS 63rd International Symposium & Exhibition | |
| Biomaterial Interfaces | Wednesday Sessions |
| Session BI+MI-WeM |
| Session: | Biosensors and Diagnostics |
| Presenter: | Lara Gamble, University of Washington |
| Authors: | L.J. Gamble, University of Washington B.M. Bluestein, University of Washington D.J. Graham, University of Washington F. Morrish, Fred Hutchinson Cancer Research Center D. Hockenbery, Fred Hutchinson Cancer Research Center |
| Correspondent: | Click to Email |
The tumor microenvironment has been associated with regulating tumor cell growth, metastatic potential, and chemotherapeutic drug resistance. However, very few techniques are capable of directly probing the tumor microenvironment on the micron scale. A new perspective is required to interpret and characterize this complex environment. Using imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS) and a mouse model with Myc-dependent inducible and regressible pancreatic β-cell neoplasia, it is possible 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 growth, protein and mitochondrial biogenesis, and metabolic alterations. Pancreatic tissues were harvested and frozen in optimal cutting temperature (OCT) at 6 days post Myc induction. 4 µm cryosections were serially cut, with one used for H&E staining, one for ToF-SIMS analysis, and another for immunohistochemistry. ToF-SIMS data was acquired on an IONTOF TOF V with pulsed 25 keV Bi3+ ion beam. Principal component analysis (PCA) of ToF-SIMS image data separated regions of tumor cells from stroma within the first principal component and revealed subtle differences in chemistry between the tumor and surrounding tissue. ToF-SIMS data suggests a preferential uptake of fatty acids 18:3, and 18:2 within the tumor. The tumor also shows an increased localization of sphingomyelin fragments and vitamin E compared to the surrounding tissue. PCA was also applied to selected tumor regions to spatially and chemically analyze within the tumor and compare chemistries between different tumor sizes. Distinct chemical differences were identified between control and 6 day Myc activated β-cell islet tissues using multivariate analysis techniques. The results from C14:0 and phosphatidylcholine fragments present within the tumor are suggestive of de novo fatty acid synthesis. This work further demonstrates the high resolution capability of ToF-SIMS as the data clearly reveals intra-tumor chemical heterogeneity as localized high intensity regions, but histologic correlations are needed to discern the purpose and function of these structures.