Trop-1 are conserved growth stimulatory molecules that mark early stages of tumor progression
Article first published online: 8 JUN 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 2, pages 452–464, 15 July 2007
How to Cite
Zanna, P., Trerotola, M., Vacca, G., Bonasera, V., Palombo, B., Guerra, E., Rossi, C., Lattanzio, R., Piantelli, M. and Alberti, S. (2007), Trop-1 are conserved growth stimulatory molecules that mark early stages of tumor progression. Cancer, 110: 452–464. doi: 10.1002/cncr.22785
- Issue published online: 29 JUN 2007
- Article first published online: 8 JUN 2007
- Manuscript Revised: 13 FEB 2007
- Manuscript Accepted: 13 FEB 2007
- Manuscript Received: 21 NOV 2006
- Fondazione of the Cassa di Risparmio della Provincia di Chieti, AIRC, Telethon, Italy. Grant Number: GGP02353
- MIUR-FIRB Postgenomica. Grant Number: RBNE0157EH
- Marie Curie Transfer of Knowledge Fellowship of the European Community's Sixth Framework Programme. Grant Number: 014541
- M.T. is the recipient of a fellowship from FIRC
- cell growth;
- cell transformation;
- tumor progression
Trop-1 is a cell-cell adhesion regulatory molecule that is overexpressed by a large fraction of tumors in man.
To identify fundamental, conserved functional features of Trop-1 in transformed cells, a search was performed for evolutionarily conserved structure, expression patterns, and function by gene cloning, DNA array and serial analysis of gene expression (SAGE), Northern and Western blotting, flow cytometry, and immunohistochemistry of sequential stages of tumor progression in experimental systems and in man.
TROP1 genes demonstrate conserved structure and promoter regions with parallel expression patterns (high expression in the small intestine and colon; lower expression in prostate, thyroid, salivary glands, breast, kidney, lung, liver, and spleen; very low levels in skin and stomach; no expression in heart, muscle, and brain). Progenitor cells of different tissues were shown to express Trop-1. Hence, the expression and functional role of Trop-1 were analyzed at successive stages of tumor progression in vitro and in vivo. The findings show that Trop-1 is expressed at early stages of tumor development, eg, in dysplastic lesions and immortalized cells, is sufficient to stimulate cell growth of expressing transformed cells, and is required for tumor growth in vivo.
The findings identify Trop-1 as a novel determinant of cell growth at early stages of tumor development and as a marker of early stages of development in normal tissues and in cancer, making this molecule a candidate for novel diagnostic and therapeutic procedures. Cancer 2007. © 2007 American Cancer Society.