Poster Presentation 35th Lorne Cancer Conference 2023

Expression and function of ADAMTS1 in ovarian cancer progression and chemoresistance (#137)

Ruth M Escalona 1 2 , Jock K Findlay 2 , George Kannourakis 1 , Nuzhat Ahmed 1 2
  1. Fiona Elsey Cancer Research Institute, Ballarat, VIC, Australia
  2. The Hudson Institute of Medical Research, Clayton, VIC, Australia

Background: ADAMTS1, a disintegrin and metalloproteinase with thrombospondin motifs 1, is essential for normal biological processes such as inflammation, organogenesis, and ovulation.  Its upregulation has been implicated in cancer development, growth, and progression.  This study analysed the expression of ADAMTS1 in epithelial serous ovarian tumours, ascites, and ascites-derived tumour cells from chemo-naïve (CN) and relapsed (CR) patients and ovarian cancer cell lines.  The role of ADAMTS1 was evaluated by knocking down the expression of ADAMTS1 by siRNA.

Methods: The levels of ADAMTS1 in primary tumours was assessed by immunohistochemistry.  The mRNA expression of ADAMTS1 in ovarian tumours and cancer cell lines were quantified by real time PCR (qRT-PCR).  Cell lines were transiently transfected with either single or pooled ADAMTS1 siRNAs. The expression of different genes after ADAMTS1 knock down was analysed at the mRNA level by qRT-PCR and at the protein level by immunofluorescence and western blot. The chemosensitivity (IC50 values) to chemotherapy treatment in the cell lines was evaluated by MTT assay.  

Results: The expression of ADAMTS1 was significantly upregulated in high-grade serous ovarian tumours compared to normal/benign ovarian tissues. At the cellular level, ADAMTS1 mRNA expression was significantly higher in epithelial CN cells than mesenchymal CN derived from ascites cancer cells.  The expression of ADAMTS1 was upregulated in response to chemotherapy treatment in cancer cell lines.

Approximately 70-80% knock down of ADAMTS1 expression by siRNA were confirmed in ADAMTS1-KD ovarian cancer cell lines at the mRNA and protein levels. Suppression of ADAMTS1 expression modulated the expression of several extracellular matrix (ECM) related genes and cellular function.

Conclusions: Our results indicate that ADAMTS1 is upregulated in tumours as ovarian cancer progresses and is upregulated after chemotherapy treatment.  Suppressing ADAMTS1 changes the the expression of several ECM related genes and modulates functions of ovarian cancer cell lines, suggesting important roles of this protein in promoting ovarian cancer progression.