Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis

• Published in: British journal of cancer Vol. 106; no. 5; pp. 896 - 903
• Main Authors: Liu, W M, Dennis, J L, Gravett, A M, Chanthirakumar, C, Kaminska, E, Coulton, G, Fowler, D W, Bodman-Smith, M, Dalgleish, A G
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2012; Nature Publishing Group
• Subjects: 631/45/127; 692/699/67/1059/99; 692/699/67/2328; Angiogenesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Cell Line, Tumor; Chemotherapy; Communication; Culture Media, Conditioned - pharmacology; Cytokines; Cytokines - biosynthesis; Cytokines - metabolism; Cytoplasmic Vesicles - physiology; Cytoplasmic Vesicles - ultrastructure; Drug Resistance; Epidemiology; Human Umbilical Vein Endothelial Cells; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Medical research; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Molecular Diagnostics; Molecular Medicine; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neovascularization, Pathologic; Oncology; Proto-Oncogene Proteins c-akt - metabolism; Transcriptome; Tumors; United Kingdom > UK; immune-modulation; tumour-supernatants; microvesicles; chemotherapy; angiogenesis; immunotherapy; Immune-modulation; Immunomodulation; Supernatant; Microvesicle; Angiogenesis; Chemotherapy; Treatment; Cancerology; Immunotherapy; Established cell line; Tumor; Neovascularization; Tumor cell
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.13

Background: There is evidence that tumours produce substances such as cytokines and microvesicular bodies bearing bioactive molecules, which support the carcinogenic process. Furthermore, chemotherapy has also been shown to modify these exudates and in doing so, neutralise their tumourigenic influence. Methods: In the current study, we have investigated the effect of chemotherapy agents on modifying the cytokine profile and microvesicular cargo of supernatants derived from cancer cell lines. In addition, we have explored the effect of these tumour-derived supernatants on angiogenesis, and how chemotherapy can alter the supernatants rendering them less pro-angiogenic. Results: Herein, we show that supernatants contain a rich cocktail of cytokines, a number of which are potent modulators of angiogenesis. They also contain microvesicular bodies containing RNA transcripts that code for proteins involved in transcription, immune modulation and angiogenesis. These supernatants altered intracellular signalling molecules in endothelial cells and significantly enhanced their tubulogenic character; however, this was severely compromised when supernatants from tumours treated with chemotherapy was used instead. Conclusion: This study suggests tumour exudates and bioactive material from tumours can influence cellular functions, and that treatment with some chemotherapy can serve to negate these pro-tumourigenic processes.