Dissection of stromal and cancer cell-derived signals in melanoma xenografts before and after treatment with DMXAA
| Autor: | Li Wang, Sofian M. Tijono, L. L. Thomsen, Peter Dunbar, Cristin G. Print, Chun-Jen J. Chen, Lai-Ming Ching, L-Cs Wang, Kimiora Henare, Sintia Winkler |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Stromal cell Transcription Genetic Xanthones medicine.medical_treatment Mice Nude Antineoplastic Agents Biology Flow cytometry Gene Knockout Techniques Mice Cell Line Tumor melanoma stroma Leukocytes medicine Animals Humans Gene Regulatory Networks Oligonucleotide Array Sequence Analysis Homeodomain Proteins Mice Knockout Regulation of gene expression medicine.diagnostic_test Gene Expression Profiling Macrophages Melanoma medicine.disease Xenograft Model Antitumor Assays cytokines Tumor Burden Up-Regulation Gene Expression Regulation Neoplastic Gene expression profiling xenografts Cytokine Oncology Cell culture DMXAA Cancer cell Stromal Cells Translational Therapeutics |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2012.63 |
| Popis: | Background: The non-malignant cells of the tumour stroma have a critical role in tumour biology. Studies dissecting the interplay between cancer cells and stromal cells are required to further our understanding of tumour progression and methods of intervention. For proof-of-principle of a multi-modal approach to dissect the differential effects of treatment on cancer cells and stromal cells, we analysed the effects of the stromal-targeting agent 5,6-dimethylxanthenone-4-acetic acid on melanoma xenografts. Methods: Flow cytometry and multi-colour immunofluorescence staining was used to analyse leukocyte numbers in xenografts. Murine-specific and human-specific multiplex cytokine panels were used to quantitate cytokines produced by stromal and melanoma cells, respectively. Human and mouse Affymetrix microarrays were used to separately identify melanoma cell-specific and stromal cell-specific gene expression. Results: 5,6-Dimethylxanthenone-4-acetic acid activated pro-inflammatory signalling pathways and cytokine expression from both stromal and cancer cells, leading to neutrophil accumulation and haemorrhagic necrosis and a delay in tumour re-growth of 26 days in A375 melanoma xenografts. Conclusion: 5,6-Dimethylxanthenone-4-acetic acid and related analogues may potentially have utility in the treatment of melanoma. The experimental platform used allowed distinction between cancer cells and stromal cells and can be applied to investigate other tumour models and anti-cancer agents. |
| Databáze: | OpenAIRE |
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