An in vitro tumor model: analysis of angiogenic factor expression after chemotherapy
| Autor: | Kristan, Keyes, Karen, Cox, Patti, Treadway, Larry, Mann, Chuan, Shih, Margaret M, Faul, Beverly A, Teicher |
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| Rok vydání: | 2002 |
| Předmět: |
Vascular Endothelial Growth Factor A
Lymphokines Paclitaxel Tumor Necrosis Factor-alpha Vascular Endothelial Growth Factors 3T3 Cells Endothelial Growth Factors Deoxycytidine Gemcitabine Carboplatin Mice Transforming Growth Factor beta Neoplasms Tumor Cells Cultured Animals Cytokines Humans Intercellular Signaling Peptides and Proteins Fibroblast Growth Factor 2 Drug Screening Assays Antitumor |
| Zdroj: | Cancer research. 62(19) |
| ISSN: | 0008-5472 |
| Popis: | Tumor tissues include malignant cells and a stroma made up of mainly inflammatory cells, endothelial cells, and fibroblasts. To differentiate the effects of treatment on angiogenic cytokine secretion in tumor tissue, exponential and stationary phase human CaKi-1 renal cell carcinoma cells, human SW2 small cell lung carcinoma cells, human umbilical vein endothelial cells (HUVECs), murine NIH-3T3 fibroblasts, and murine RAW264.7 macrophages were exposed to gemcitabine, paclitaxel, carboplatin, and the protein kinase Cbeta inhibitor LY317615, and secretion (24 h) of tumor necrosis factor-alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-beta was determined by a Luminex FlowMetrix assay. After 72 h of exposure, exponential RAW, 3T3, and SW2 cells were sensitive to gemcitabine; exponential and stationary SW2 and HUVECs were sensitive to paclitaxel; and exponential and stationary HUVECs were most sensitive to LY317615. None of the cells secreted detectable tumor necrosis factor-alpha. Generally, exponential cells secreted higher levels of cytokines than stationary cells (stationary cells secreted approximately 10 times less TGF-beta). Only malignant cells secreted VEGF (80-300 pg/10(6) cells). VEGF secretion by exponential SW2 cells decreased in an anticancer agent concentration-dependent manner. Every cell type secreted TGF-beta (40-700 pg/10(6) cells). Exponential 3T3, RAW, CaKi-1, and SW2 cells secreted the most TGF-beta, and levels did not decrease with treatment. Only CaKi-1, SW2, and HUVECs secreted bFGF (0.5-50 pg/10(6) cells). CaKi-1 cells increased secretion of bFGF with therapy. Although malignant cells alone secreted VEGF, stromal cells secreted TGF-beta and bFGF at levels comparable with or greater than malignant cells and thus may be important contributors to tumor growth and progression. |
| Databáze: | OpenAIRE |
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