In vivo inhibition of angiogenesis and induction of apoptosis by retinoic acid in squamous cell carcinoma

Emmanuelle D.E. Liaudet-Coopman, Guy J. Berchem, Anton Wellstein*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

44 Citations (Scopus)

Abstract

Retinoids inhibit the growth and reverse aberrant differentiation of squamous cell carcinoma (SCC) cells in vitro. To investigate the potential mechanisms of antitumor activity of retinoids in vivo, we used the cervical SCC cell line ME-180 as a s.c. tumor xenograft in athymic nude mice. After s.c. injection, tumor cells were allowed to form visible tumors and antitumor activity of all-trans-retinoic acid (tRA) was studied. tRA was administered daily for a 1-week or a 2-week period at 60 mg/kg/day. Tumor specimens were then analyzed using immunohistochemical staining for the number of blood vessels and apoptotic cells and for proliferating cell nuclear antigen expression. Furthermore, we studied the effect of the tRA treatment on the expression of a binding protein for fibroblast growth factors (BP; GenBank accession no. M60047) that is a candidate angiogenesis modulator in SCC (F. Czubayko et al., J. Biol. Chem., 269: 28243-28248, 1994). We found that in vivo tRA treatment reduces BP expression in SCC xenografts, inhibits their angiogenesis, induces apoptosis of the tumor cells, and leads to a decrease of the tumor growth rate. We speculate that the tRA down-regulation of BP is responsible for the reduction of angiogenesis.

Original languageEnglish
Pages (from-to)179-184
Number of pages6
JournalClinical Cancer Research
Volume3
Issue number2
Publication statusPublished - 1997
Externally publishedYes

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