α(2)-Adrenoceptors enhance cell proliferation and mammary tumor growth acting through both the stroma and the tumor cells
| Autor: | Ariana, Bruzzone, Cecilia Pérez, Piñero, Paola, Rojas, Marina, Romanato, Hugo, Gass, Claudia, Lanari, Isabel A, Lüthy |
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| Rok vydání: | 2010 |
| Předmět: |
Mice
Inbred BALB C Mammary Neoplasms Experimental Mice Nude Yohimbine Breast Neoplasms Epithelial Cells Adrenergic alpha-2 Receptor Antagonists Fibroblasts Immunohistochemistry Clonidine Cell Line Mice Catecholamines Receptors Adrenergic alpha-2 Cell Line Tumor Adrenergic alpha-2 Receptor Agonists Disease Progression Animals Humans Female Stromal Cells Cell Proliferation |
| Zdroj: | Current cancer drug targets. 11(6) |
| ISSN: | 1873-5576 |
| Popis: | We have previously described enhanced human breast cancer cell proliferation and mouse mammary tumor growth induced by α(2)-adrenoceptor (α(2)-AR) expression in epithelial cells. The aim of the present work was to assess if stromal fibroblasts can contribute to this effect. α(2)-AR expression was assessed by immunocytochemistry and immunohistochemistry, cell proliferation by [(3)H]-Thymidine incorporation and tumor growth by measuring with caliper. All tested mouse and human fibroblasts expressed at least two α(2)-AR subtypes and α(2)-adrenergic agonists enhanced fibroblast proliferation. In vivo, the α(2)-adrenergic agonist clonidine significantly enhanced tumor growth. The α(2)-adrenergic antagonist rauwolscine reversed this effect, but when administered alone, significantly inhibited tumor growth. Clonidine significantly stimulated cell proliferation in the epithelial-enriched fraction, the cancer associated fibroblast-enriched fraction and the co-culture of both fractions in primary cultures from both tumors (IBH-4 and IBH-6). Rauwolscine reversed clonidine stimulation in every fraction. However, when incubated alone, the inhibitory effect was observed in fractions from IBH-4 tumors but not from IBH-6 tumors. These experiments show that fibroblasts from tumor stroma are also influenced by α(2)-adrenergic compounds through the α(2)-ARs expressed in these cells. Moreover, the α(2)-adrenergic antagonist rauwolscine could eventually block in both epithelial and stromal cells, the mitogenic effect of catecholamines released during stress, providing a potential additional treatment for breast cancer patients. Chemists synthesizing adrenergic compounds should consider their action in breast cancer patients. |
| Databáze: | OpenAIRE |
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