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Unformatted text preview: k). B) Histologic section (hematoxylin and eosin stained, magnification
200×) of a lentiginous form of malignant melanoma in a human skin graft on a SCID mouse. The graft had received a total of seven injections
of bFGF/Ad5 and 26 UV-B irradiations. Note the hyperplastic atypical melanocytic cells (arrows) in the epidermis in a dense lentiginous growth
pattern. Photographs courtesy of Carolla Berking. Figure 2. Altered cadherin expression during melanoma progression. The progression of melanoma along with its accompanying change in
cadherin expression is illustrated. A) Keratinocytes and melanocytes both express E-cadherin. Through E-cadherin expression, keratinocytes
dictate melanocyte behavior. B) While keratinocytes continue to express E-cadherin, early melanomas begin to lose expression of E-cadherin
and escape keratinocyte control. C) More advanced melanomas begin to express N-cadherin and may interact with other cells that express
N-cadherin, like fibroblasts and endothelial cells. Perlis, Herlyn
predominantly target tumor-infiltrating endothelial cells.
In melanoma, we expect dual targeting for normal and
Recent advances in the understanding of the biology of
melanoma promise to provide not just keys to further
knowledge per se, but also clues to novel and more effective therapies. Models employing UV-B light to induce
melanoma in human skin promise to lead to significant
advancements in prevention. Scientists can now better dissect the specific mechanisms of UV-B-radiation-induced
melanoma genesis as well as observe key steps in tumor initiation and progression. Findings from studies of the B-raf
gene illustrate that broad screening approaches have a value
for identifying new targets for therapy by developing spe- 186 cific inhibitors. Better knowledge of the intricate cellular
interactions in melanoma provides us with new clues to
developing novel therapies to reestablish control of malignant cells by keratinocytes. We may even develop strategies in which small molecules mimic keratinocytes and
maintain lasting control.
Models can be used to test the efficacy of sunscreens
or anticipate the effects of ozone depletion on melanoma
rates. Models confirm the importance of public health initiatives encouraging the use of sunblocks. Insights into the
roles of E- and N-cadherins should prove similarly valuable. These cell adhesion molecules may serve both as
prognostic markers for disease behavior and sites for possible therapeutic interventions. Increased knowledge about
apoptotic pathways should also offer hope for new and
effective treatments. R EFERENCES
1 Hall HI, Miller DR, Rogers JD et al. Update on the incidence
and mortality from melanoma in the United States. J Am Acad
Dermatol 1999;40:35-42. 12 Klein-Parker HA, Warshawski L, Tron VA. Melanocytes in
human skin express bcl-2 protein. J Cutan Pathol 1994;21:297301. 2 Greenlee RT, Hill-Harmon MB, Murray T et al. Cancer
statistics, 2001. CA Cancer J Clin 2001;51:15-36. 1...
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This document was uploaded on 03/06/2014.
- Spring '14