Ultrasound backscatter microscope analysis of mouse melanoma progression.

The incidence and mortality rate of cutaneous melanoma continue to increase throughout the world, making the study of melanoma biology an important area of current research. While recent breakthroughs in transgenic mouse technology have led to promising mouse skin models of melanoma, there is presently no technique available for quantitatively studying subsurface melanoma progression, in vivo. We demonstrate the first application of an imaging method called ultrasound backscatter microscopy (UBM) for imaging early murine melanomas with spatial resolution of 30 microns axial and 60 microns lateral. Murine B16 F10 melanomas have been imaged from their earliest detection, over several days, until they are 2 to 5 mm in diameter. Melanoma dimensions measured by UBM were found to be in excellent agreement with those determined histopathologically on the excised tumours. The relative rms errors in UBM-determined melanoma height and width were found to be 8.7% and 4.2%, respectively. The mean rate of increase in tumour height of early murine melanoma was found to be 0.37 +/- 0.06 mm/day. Computer-generated volumetric renderings of melanomas have been produced from three-dimensional image data, allowing quantitative comparisons of tumour volumes to be made. Using a priori assumptions of ellipsoid tumour shape, the relative error in UBM-determined volume was shown to be less than 17%. These results should be of considerable interest to investigators studying melanoma biology using mouse skin models, and have implications in the use of high frequency ultrasound imaging for the clinical assessment of cutaneous melanoma.

Effect of ultraviolet-inducible cytokines on melanoma growth in vivo: stimulation of melanoma growth by interleukin-1 and -6.

Ultraviolet light of wavelengths 280-320 nm (UVB) can induce transcription of cytokine mRNAs and increase expression of the corresponding proteins in the epidermis. In particular, UVB can stimulate keratinocyte synthesis of interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta). Several of these cytokines can influence the growth of tumour cells as well as the host response to these tumours. In this study we examined the effect of IL-1, IL-6, IL-8, TNF-alpha and TGF-beta on the growth of melanoma in vivo and in vitro, using the murine B16 melanoma and its syngeneic host, the C57BL/6 mouse. Mice were injected with 0.1-1.5 micrograms of recombinant cytokine subcutaneously every other day following a subcutaneous injection of 1 x 10(5) B16 cells (F-10 clone). In this model, tumours appeared within 12-14 days, and IL-1 and IL-6 stimulated tumour growth in vivo. TNF-alpha, TGF-beta, IL-2 and IL-8 had no significant effect. In contrast to the in vivo effects, TNF-alpha inhibited B16 cell growth in vitro and IL-6 stimulated B16 cell growth. The in vivo IL-1 effect on tumour growth in mice was examined in greater detail. IL-1-treated animals showed tumours approximately 5-fold greater in size than those of the control animals. The IL-1-treated animals also showed highly vascularized tumours that invaded underlying muscle tissue more rapidly than controls. These tumors also showed a strong positive reaction with antibody to intercellular adhesion molecule-1.(ABSTRACT TRUNCATED AT 250 WORDS)