ORIGINAL ARTICLES: Basic researchKeratinocytes drive melanoma invasion in a reconstructed skin modelVan Kilsdonk, Jeroen W.J.a; Bergers, Miekeb; Van Kempen, Léon C.L.T.c; Schalkwijk, Joostb; Swart, Guido W.M.aAuthor Information aDepartment of Biomolecular Chemistry, Faculty of Science, Radboud University Nijmegen Departments of bDermatology cPathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Correspondence to Jeroen W.J. Van Kilsdonk, PhD, Department of Dermatology, NCMLS, Radboud University Nijmegen Medical Centre, Nijmegen, PO Box 9101, Nijmegen NL-6500 HB, The Netherlands Tel: +31 24 3613272; fax: +31 24 3541184; e-mail: [email protected] Present address: Jeroen W.J. Van Kilsdonk, Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands Received 8 December 2009 Accepted 23 June 2010 Melanoma Research: October 2010 - Volume 20 - Issue 5 - p 372-380 doi: 10.1097/CMR.0b013e32833d8d70 Buy Metrics Abstract Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling of the extracellular matrix including basement membranes. Here we used a reconstructed skin model to investigate melanoma growth and invasion in vitro. Using this model we show that the dermoepidermal basement membrane prevents the invasion of metastatic melanoma BLM and MV3 cells in the absence of a stratified epidermis. In the reconstructed skin model, matrix metalloproteinase-9, a protease activated early in melanoma development, is secreted by the keratinocytes and subsequently activated by an unknown soluble factor secreted by the melanoma cells. The dynamic interplay between keratinocytes and melanoma cells is further shown by an altered growth pattern of melanoma cells and the finding that a reconstructed epidermis induces invasion. Overall, our findings show that the invasive behavior of melanoma cells is determined by the melanoma cells themselves, but that the interplay between surrounding keratinocytes and the melanoma cells plays an important role in melanoma invasion. © 2010 Lippincott Williams & Wilkins, Inc.