Journal article

Targeting platelets for improved outcome in KRAS-driven lung adenocarcinoma

Stephanie R Hyslop, Marliese Alexander, Alesha A Thai, Ariena Kersbergen, Andrew J Kueh, Marco J Herold, Jason Corbin, Pradnya Gangatirkar, Ashley P Ng, Benjamin J Solomon, Warren S Alexander, Kate D Sutherland, Emma C Josefsson

Oncogene | Springer Nature | Published : 2020

Abstract

Elevated platelet count is associated with poor survival in certain solid cancers, including lung cancer. In addition, experimental transplantation of cancer cell lines has uncovered a role for platelets in blood-borne metastasis. These studies, however, do not account for heterogeneity between lung cancer subtypes. Subsequently, the role of platelets in the major subtypes of non-small cell lung cancer (adenocarcinoma (ADC) and squamous cell carcinoma (SqCC)) is not fully understood. We utilised an autochthonous KrasLSL-G12D/+;p53flox/flox mouse model of lung ADC together with genetic models of thrombocytopenia to interrogate the role of platelets in lung cancer growth and progression. While..

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Grants

Awarded by National Health and Medical Research Council


Awarded by Victorian Cancer Agency


Awarded by Leukemia and Lymphoma Society


Funding Acknowledgements

We thank Prof Benjamin Kile for generously providing Bcl-x<SUP>Plt20</SUP> mice and A/Prof Marie-Liesse Asselin-Labat for kindly sharing cell lines. We thank Janelle Lochland, Dr Amanda Au, Nicole Lynch, Stephanie Bound, Keti Stoev, Rebekah Meeny and Shannon Oliver for outstanding assistance and Prof Doug Hilton for helpful discussions. Ann Officer facilitated data collection for the Thoracic Malignancies Cohort Study and Him Ahmad assisted with patient pathology data collation. This work was supported by Australian National Health and Medical Research Council Project, Ideas, and Program Grants (1079250 ECJ, 1113577, 1122783 APN, 1186575 MJH, 1159658 MJH), Fellowships (1058344 WSA, 1156095 MJH), an Independent Research Institutes Infrastructure Support Scheme Grant (9000220), and a Victorian State Government Operational Infrastructure Support Grant. ECJ is the recipient of a fellowship from the Lorenzo and Pamela Galli Charitable Trust. SRH is the recipient of an Australian Postgraduate Award from the University of Melbourne. KDS is supported by a Victorian Cancer Agency Mid-Career Fellowship (MCRF18003) and the Peter and Julie Alston Centenary Fellowship. The generation of the NSG Mpl-/-mice was supported by the Australian Phenomics Network, the Leukemia and Lymphoma Society (LLS SCOR 7001-13 MJH), and the Australian Government through the National Collaborative Research Infrastructure Strategy program.