The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 305K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wesley, U. V.
Right arrow Articles by Houghton, A. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wesley, U. V.
Right arrow Articles by Houghton, A. N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1999/8/311/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 3, August 2, 1999 311-322

Original Article

A Role for Dipeptidyl Peptidase IV in Suppressing the Malignant Phenotype of Melanocytic Cells

Umadevi V. Wesleya, Anthony P. Albinoa, Shakuntala Tiwaria, and Alan N. Houghtona

a From the Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division, Weill Graduate School of Medical Sciences of Cornell University, New York 10021
Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.212-794-4352212-639-7595

a-houghton{at}ski.mskcc.org

Dipeptidyl peptidase IV (DPPIV) is a cell surface peptidase expressed by normal melanocytes, epithelial cells, and other cells. Malignant cells, including melanomas and carcinomas, frequently lose or alter DPPIV cell surface expression. Loss of DPPIV expression occurs during melanoma progression at a stage where transformed melanocytes become independent of exogenous growth factors for survival. Tetracycline-inducible expression vectors were constructed to express DPPIV in human melanoma cells. Reexpressing DPPIV in melanoma cells at or below levels expressed by normal melanocytes induced a profound change in phenotype that was characteristic of normal melanocytes. DPPIV expression led to a loss of tumorigenicity, anchorage-independent growth, a reversal in a block in differentiation, and an acquired dependence on exogenous growth factors for cell survival. Suppression of tumorigenicity and reversal of a block in differentiation were dependent on serine protease activity, assessed using mutant DPPIV molecules containing serine->alanine substitutions. Surprisingly, dependence on exogenous growth factors was not dependent on serine protease activity. Reexpression of either wild-type or mutant DPPIV rescued expression of a second putative cell surface serine peptidase, fibroblast activation protein {alpha}, which can form a heterodimer with DPPIV. This observation suggests that rescue of fibroblast activation protein {alpha} may play a role in regulating growth of melanocytic cells. These results support the view that downregulation of DPPIV is an important early event in the pathogenesis of melanoma.

Key Words: melanoma • fibroblast activating protein {alpha} • serine protease • tumorigenicity • differentiation

1used in this paper: dox, doxycycline; DPPIV, dipeptidyl peptidase IV; FAP{alpha}, fibroblast activating protein {alpha}; TRP, tyrosinase-related protein; TUNEL, TdT-mediated dUTP-biotin nick-end labeling

A.P. Albino's present address is American Health Foundation, 1 Dana Rd., Valhalla, NY 10595.

© 1999 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS