G GOBE1, Q NGUYEN2, R MORET2, C MORAIS1, X ZHANG2, G MARESH2, L HELMERS2, S TALWAR3, M LATSIS3, M VARIANO3, D CANTER3, S BARDOT3, L LI1
1University Of Queensland, Brisbane, Australia, 2Institute of Translational Cancer Research, Ochsner Health System, New Orleans, USA, 3Department of Urology, Ochsner Health System, New Orleans, USA
Aim: To determine the molecular mechanisms by which lymph node (LN) stromal cells stimulate growth and progression of renal cell carcinomas (RCC).
Introduction: RCC are the most common solid tumour of the adult kidney, with a cancer specific mortality of 30–40%. LN metastases are strongly negative for RCC prognosis. RCC metastases are incurable and affect up to 25% of patients. In our previous experiments using orthotopic xenograft models, LN stromal cells (HK cells) enhanced RCC tumor progression, with growth of the RCC cell line ACHN dependent on HK cells, and SN12K1 RCC cells relatively independent of HK cells in tumour formation, tumour growth and distant organ metastasis.
Methods: To investigate alterations in protein expression, RCC cells lines (ACHN and SN12K1) were cultured with or without HK cell supernatant and cell lysates were subjected to proteomic mass spectroscopy analysis (TRI Proteomics Facility, Australia). Significantly-altered protein markers were selected using data and bioinformatics analysis and information from the web-based proteinatlas database.
Results: 1540 proteins were detected by proteomic analysis. 128 proteins were present in both cell lines. In response to HK cell supernatant treatment, the following 10 novel cancer progression-related proteins were significantly differentially expressed: CTSD, SAMHD1, FAM114A1, RFC5, NAPA, SRP68, SNX6, AIMP1, PSMD6, and YWHAE. Quantitative analysis by Western blotting validated the differential expression of these proteins in response to the conditioned medium from stromal cells.
Conclusions: The presence of conditioned media from HK LN stromal cells altered expression of specific cancer proteins in RCC. Further studies into the pathways affected by these proteins and, subsequently, blocking those pathways may lead to novel treatments for RCC patients.
Glenda Gobe is a molecular biologist with a well-established international reputation in kidney disease research. She has published widely on research into kidney atrophy and regeneration, fibrosis, inflammation, and kidney cancer. She has over 200 peer-reviewed publications and many highly-cited articles. Dr Gobe teaches biomedical sciences and pathology and supervises multiple PhD students. She is Co-Director of the Centre for Kidney Disease Research at the School of Biomedical Sciences, Faculty of Medicine and Translational Research Institute, the University of Queensland.