Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer

Cathcart, Mary Clare, Gately, Kathy, Cummins, Robert, Drakeford, Clive, Kay, Elaine, O'Byrne, Kenneth J., & Pidgeon, Graham P. (2014) Thromboxane synthase expression and correlation with VEGF and angiogenesis in non-small cell lung cancer. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1842(5), pp. 747-755.

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Abstract

Background

Thromboxane synthase (TXS) metabolizes prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with angiogenesis and poor outcome. TXS has been identified as a potential therapeutic target in NSCLC. This study examines a link between TXS expression, angiogenesis, and survival in NSCLC.

Methods

TXS and VEGF metabolite levels were measured in NSCLC serum samples (n=46) by EIA. TXB2 levels were correlated with VEGF. A 204-patient TMA was stained for TXS, VEGF, and CD-31 expression. Expression was correlated with a range of clinical parameters, including overall survival. TXS expression was correlated with VEGF and CD-31. Stable TXS clones were generated and the effect of overexpression on tumor growth and angiogenesis markers was examined in-vitro and in-vivo (xenograft mouse model).

Results

Serum TXB2 levels were correlated with VEGF (p<0.05). TXS and VEGF were expressed to a varying degree in NSCLC tissue. TXS was associated with VEGF (p<0.0001) and microvessel density (CD-31; p<0.05). TXS and VEGF expression levels were higher in adenocarcinoma (p<0.0001) and female patients (p<0.05). Stable overexpression of TXS increased VEGF secretion in-vitro. While no significant association with patient survival was observed for either TXS or VEGF in our patient cohort, TXS overexpression significantly (p<0.05) increased tumor growth in-vivo. TXS overexpression was also associated with higher levels of VEGF, microvessel density, and reduced apoptosis in xenograft tumors.

Conclusion

TXS promotes tumor growth in-vivo in NSCLC, an effect which is at least partly mediated through increased tumor angiogenesis.

Impact and interest:

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ID Code: 67768
Item Type: Journal Article
Refereed: Yes
Keywords: Non-small cell lung cancer, Thromboxane synthase, Angiogenesis, VEGF, CD-31
DOI: 10.1016/j.bbadis.2014.01.011
ISSN: 0006-3002
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 26 Feb 2014 00:54
Last Modified: 11 Sep 2014 01:37

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