Poster Presentation 26th Lorne Cancer Conference 2014

Characterisation of ADAMTS15: a potential tumour suppressor gene in Prostate cancer (#113)

Marley J Binder 1 , Elizabeth D Williams 2 , Ken Opeskin 3 , Scott McCoombe 1 , Daniel R McCulloch 1
  1. Deakin University, Waurn Ponds, VIC, Australia
  2. University of Melbourne, St. Vincents hopsital, Melbourne, Vic , Australia
  3. St. Vincents Pathology , Melbourne , Vic, Australia

Introduction: ADAMTS gene family includes the versican cleaving proteoglycanases ADAMTS5 and ADAMTS15, which are expressed in prostate cancer (PrCa) cell lines1. Increased versican (VCAN) expression in metastatic PrCa cell lines decreases cell adhesion and increases their migratory capacity 2. ADAMTS15 is a putative tumour suppressor gene and ADAMTS5 may regulate angiogenesis 3,4. We hypothesise that ADAMTS5 and ADAMTS15 are key regulators of PrCa progression. Aims: (1) To examine expression and growth factor regulation of ADAMTS5 and ADAMTS15 in PrCa cell lines, (2) to determine the effect of ADAMTS5 and ADAMTS15 on PrCa cell migration and proliferation, and (3) to determine the localisation of ADAMTS5 and ADAMTS15 in PrCa patient biopsies. Results: LNCaP (early-stage) and PC-3 (late-stage) PrCa cell lines expressed ADAMTS5, ADAMTS15 and VCAN mRNA. Treatment of LNCaPs with 100 ng/µl EGF (24 h, P=<0.001) led to a significant up-regulation of ADAMTS5 mRNA (3-fold) determined by qPCR. Scratch wound assays of PC-3 cell monolayers treated with exogenous ADAMTS5 showed increased cell migration (6 h, P=<0.05), whilst, paradoxically, exogenous treatment ADAMTS15 showed decreased cell migration (6 h, P=<0.05). Stably transfected cell lines demonstrated significantly decreased proliferation (48h, P=<0.01) (LNCaPs expressing ADAMTS15EA - catalytically inactive) with a trend towards decreased cell proliferation in the case of LNCaPs expressing wildtype ADAMTS15. A similar trend was also seen in PC3 cells expressing either ADAMTS15 or ADAMTS15EA. In PrCa biopsies ADAMTS5 and ADAMTS15 were predominantly localised to the stroma of both low and high grade PrCa. Conclusions: ADAMTS15 has the potential to decrease PrCa cell proliferation and to inhibit collective cell migration while ADAMTS5 might promote PrCa progression. This is the first report of, to our knowledge, ADAMTS5 and ADAMTS15 localisation in PrCa specimens. Further studies now are required to investigate the role of ADAMTS5 and ADAMTS15, and their relationship to versican throughout PrCa progression.

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