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Trop‐1 are conserved growth stimulatory molecules that mark early stages of tumor progression
Author(s) -
Zanna Paola,
Trerotola Marco,
Vacca Giovanna,
Bonasera Veronica,
Palombo Barbara,
Guerra Emanuela,
Rossi Cosmo,
Lattanzio Rossano,
Piantelli Mauro,
Alberti Saverio
Publication year - 2007
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.22785
Subject(s) - biology , progenitor cell , tumor progression , cancer , cell growth , cancer research , pathology , gene expression , stem cell , gene , microbiology and biotechnology , medicine , genetics
BACKGROUND. Trop‐1 is a cell‐cell adhesion regulatory molecule that is overexpressed by a large fraction of tumors in man. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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.