Melanoma development and progression: a conspiracy between tumor and host.
While a genome-centric paradigm in human cancer development was useful for the understanding of some malignancies such as leukemias, causative molecular defects intrinsic to melanocytes have not been defined in the majority of human melanomas. Recent work, however, has shown that regulatory signals governing melanocytic cell growth and differentiation may originate from the surrounding host cells either directly through physical contact or indirectly through soluble factors and extracellular matrix molecules. In this review, we present experimental systems useful for dissecting melanoma-host interactions and highlight evidence that the tumor microenvironment contributes to the oncogenic process. Thus, melanomagenesis is not merely an act of a single outlaw but a conspiracy orchestrated by multiple partners in the neighborhood who come into play in a precise spatiotemporal order. Defining intercellular molecular dialogues in human skin promises to provide key information for the development of novel treatment strategies that target the functional unit of stroma and tumor.
Hsu
Mei-Yu
MY
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4283, USA.
Meier
Friedegund
F
Herlyn
Meenhard
M
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018920:Coculture Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism*; D016038:Skin Transplantation; D017768:Skin, Artificial
D015820:Cadherins; D015815:Cell Adhesion Molecules