Gastrin Exerts Pleiotropic Effects on Human Melanoma Cell Biology<sup><a href="#FN1" rid="FN1" class=" fn">1</a></sup>

Véronique Mathieu

Tatjana Mijatovic

Marc van Damme

Robert Kiss

Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels (ULB), Brussels, Belgium

Address all correspondence to: Robert Kiss, PhD, Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels (ULB), Campus de la Plaine, Boulevard du Triomphe, Brussels B-1050, Belgium. E-mail: eb.ca.blu@ssikr

Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels (ULB), Brussels, Belgium

Received 2005 Jun 2; Revised 2005 Jul 28; Accepted 2005 Jul 28.

Abstract

The effects of gastrin (G17) on the growth and migration factors of four human melanoma cell lines (HT-144, C32, G-361, and SKMEL-28) were investigated. The expression patterns of cholecystokinin (CCK)_A, CCK_B, and CCK_C gastrin receptors were investigated in these cells and in seven clinical samples by means of reverse transcription polymerase chain reaction. Melanoma cells appear to express mRNA for CCK_C receptors, but not for CCK_A or CCK_B receptors. Although gastrin does not significantly modify the growth characteristics of the cell lines under study, it significantly modifies their cell migration characteristics. These modifications occur at adhesion level by modifying the expression levels of α_v and β₃ integrins, at motility level by modifying the organization of the actin cytoskeleton, and at invasion level by modifying the expression levels of matrix metalloproteinase 14. We recently demonstrated the presence of CCK_B receptors in mouse endothelial cells involved in glioblastoma neoangiogenesis. Chronic in vivo administration of a selective CCK_B receptor antagonist to mice bearing xenografts of human C32 melanoma cells significantly decreased levels of neo-angiogenesis, resulting in considerable delays in the growth of these C32 xenografts. In conclusion, our study identifies the pleiotropic effects of gastrin on melanoma cell biology.

Keywords: melanoma, gastrin, motility, invasion, apoptosis resistance

Abstract

Abbreviations

CCK	cholecystokinin
G17	gastrin
IGF	insulin-like growth factor
IL-8	interleukin-8
MMP	matrix metalloproteinase
MRDO	maximum relative distance to the origin
MTT	(3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
PCR	polymerase chain reaction
PI3-K	phosphoinositide 3-kinase

Abbreviations

Footnotes

^{The present study has been carried out on the basis of grants awarded by the Fonds National de la Recherche Scientifique (FNRS, Belgium) and the}Fonds Yvonne Boël (Brussels, Belgium).

^{R.K. is a Director of Research with the Fonds National de la Recherche Scientifique (FNRS, Belgium).}

Footnotes

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