Pharmaceutical Sciences Faculty Publications
Caffeine Suppresses Metastasis in a Transgenic Mouse Model: A Prototype Molecule for Prophylaxis of Metastasis
Document Type
Article
Publication Date
1-1-2004
Journal Title
Clinical & Experimental Metastasis
ISSN
0262-0898
Volume
21
Issue
8
First Page
719
Last Page
735
DOI
10.1007/s10585-004-8251-4
PubMed ID
16035617
Abstract
A significant fraction of cancer patients have occult disseminated tumors at the time of primary diagnosis, which usually progress to become clinically relevant lesions. Since the majority of cancer mortality is associated with metastatic disease, the ability to inhibit the growth of the secondary tumors would significantly reduce cancer-related morbidity and mortality. We have investigated whether caffeine, which has been shown to suppress tumor cell invasiveness and experimental metastasis, can suppress metastasis in a spontaneous transgene-induced mammary tumor model. Chronic exposure to caffeine prior to the appearance of palpable mammary tumors significantly reduced both tumor burden and metastatic colonization. However, when caffeine exposure began after the appearance of frank tumors, caffeine suppressed metastasis without changing primary tumor burden. The means by which caffeine suppressed metastatic activity may be associated with inhibition of malignant transformation of mammary epithelial cells, inhibition of conversion of dormant tumor cells to micrometastases, micrometastases to macrometastases, or inhibition of tumor cell adhesion and motility. Gene and protein expression patterns resulting from caffeine treatment showed that metastasis suppression may be associated with up-regulation the mRNA expression of multiple extracellular matrix genes, including Fbln1, Bgn, Sparc, Fbn1, Loxl1, Colla1, Col3a1, Col5a1, ColS5a2, ColSa3, Col6a1, Col6a2, and Col6a3. These data suggested that caffeine or other methyl xanthine derivatives may improve the clinical outcome in patients prior to and following the diagnosis of metastatic disease, and could potentially reduce the morbidity and mortality associated with disseminated tumors.
Keywords
Antigens, polyomavirus transforming, biomarkers, tumor, caffeine, central nervous system stimulants, disease models, electrophoresis, gel, gene expression neoplastic, lung neoplasms, mammary neoplasms, experimental, mammary tumor virus, transgenic, tumor burden, tumor cells, cultured
Recommended Citation
Yang, Haiyan; Rouse, Jessica; Lukes, Luanne; Lancaster, Mindy; Veenstra, Timothy D.; Zhou, Ming; Shi, Ying; Park, Yeong-Gwan; and Hunter, Kent, "Caffeine Suppresses Metastasis in a Transgenic Mouse Model: A Prototype Molecule for Prophylaxis of Metastasis" (2004). Pharmaceutical Sciences Faculty Publications. 443.
https://digitalcommons.cedarville.edu/pharmaceutical_sciences_publications/443