Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models.

Autor: Bridgeman VL; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Vermeulen PB; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.; Translational Cancer Research Unit (TCRU), GZA Hospitals St Augustinus, Antwerp, Belgium., Foo S; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Bilecz A; 2nd Institute of Pathology, Semmelweis University, Budapest, Hungary., Daley F; Breast Cancer Now Histopathology Core Facility, The Royal Marsden, London, UK., Kostaras E; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Nathan MR; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Wan E; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.; The Royal Marsden, London, UK., Frentzas S; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.; The Royal Marsden, London, UK., Schweiger T; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Hegedus B; Department of Thoracic Surgery, Ruhrlandklinik Essen, University Hospital of University Duisburg-Essen, Germany.; MTA-SE Molecular Oncology Research Group, Hungarian Academy of Sciences, Budapest, Hungary., Hoetzenecker K; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria., Renyi-Vamos F; Department of Thoracic Surgery, Semmelweis University-National Institute of Oncology, Budapest, Hungary., Kuczynski EA; Department of Medical Biophysics, University of Toronto, Toronto, Canada., Vasudev NS; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.; The Royal Marsden, London, UK.; Cancer Research UK Centre, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, UK., Larkin J; The Royal Marsden, London, UK., Gore M; The Royal Marsden, London, UK., Dvorak HF; Beth Israel Deaconess Medical Center, Boston, MA, USA., Paku S; 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.; Tumour Progression Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary., Kerbel RS; Department of Medical Biophysics, University of Toronto, Toronto, Canada.; Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Canada., Dome B; Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.; Department of Thoracic Surgery, Semmelweis University-National Institute of Oncology, Budapest, Hungary.; National Koranyi Institute of Pulmonology, Budapest, Hungary.; Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Austria., Reynolds AR; Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
Jazyk: angličtina
Zdroj: The Journal of pathology [J Pathol] 2017 Feb; Vol. 241 (3), pp. 362-374. Date of Electronic Publication: 2016 Dec 29.
DOI: 10.1002/path.4845
Abstrakt: Anti-angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti-angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre-existing vessels from surrounding tissue (vessel co-option). As anti-angiogenic therapies were designed to target only new blood vessel growth, vessel co-option has been proposed as a mechanism that could drive resistance to anti-angiogenic therapy. However, vessel co-option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti-angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co-option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co-opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co-opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co-option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co-option mediates resistance to the anti-angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co-option in lung metastases occurs through at least three distinct mechanisms, that vessel co-option occurs frequently in lung metastases, and that vessel co-option could mediate resistance to anti-angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co-option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
(© 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)
Databáze: MEDLINE
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