Human melanoma progression in skin reconstructs - Biological significance of bFGF

被引:175
作者
Meier, F
Nesbit, M
Hsu, MY
Martin, B
Van Belle, P
Elder, DE
Schaumburg-Lever, G
Garbe, C
Walz, TM
Donatien, P
Crombleholme, TM
Herlyn, M
机构
[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA USA
[3] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA
[4] Univ Tubingen, Dept Dermatol, Tubingen, Germany
关键词
D O I
10.1016/S0002-9440(10)64719-0
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Celts in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.
引用
收藏
页码:193 / 200
页数:8
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