Histological basis of MR/optical imaging of human melanoma mouse xenografts spanning a range of metastatic potentials

Abstract

Predicting tumor aggressiveness will greatly facilitate cancer treatment. We have previously reported investigations utilizing various MR/optical imaging methods to differentiate human melanoma mouse xenografts spanning a range of metastatic potentials. The purpose of this study was to explore the histological basis of the previously reported imaging findings. We obtained the cryogenic tumor sections of three types of human melanoma mouse xenografts with their metastatic potentials falling in the rank order A375P<A375M<C8161. Both H&E and DAPI counter-stained TUNEL analysis showed distinct core-rim difference in aggressive tumors, while the core has apparently many viable cells forming structure of vascular-like networks and the rim appears viable-cell dense. The least aggressive ones (A375P) are relatively more homogenous without distinct core-rim difference. However, our previous study showed the core of more aggressive melanoma has higher Fp/NADH redox ratio, indicative of nutritional deprivation. Additionally, the low perfusion/blood vessel permeability measured previously by DCE-MRI indicated these cells should be under starvation presumably accompanied with more cell death. Thus, it remains an open question what the survival status of the cells in the core of more aggressive melanoma is. We are currently investigating whether these cells are in autophagic state, a possible cell survival mechanism under starvation conditions.

Figure 1.

(a)-(h) Photo-stitched images of a tumor section and (i)-(j) expanded view of a core area of the most aggressive C8161 showing few apoptotic cells (20X). (a) & (b) H&E staining image (40X) of tumor sections of A375M (a) and A375P (b); FITC (c) and DAPI (d) of A375M and FITC (e) and DAPI (f) of A375P; FITC (g) and DAPI (h) of C8161; (i) FITC of C8161, and (j) DAPI of C8161. The diameter of the tumors shown here is greater than 11 mm. The strong fluorescence in Figure 1(c) is not specific FITC-signal for apoptosis, rather it maybe tissue autofluorescence.