AB141. Novel clinical roles for junctional adhesion molecule—a in breast cancer progression
Session 10: General III

AB141. Novel clinical roles for junctional adhesion molecule—a in breast cancer progression

Emily Josephine Rutherford, Catherine Richards, Arnold David Konrad Hill, Ann Hopkins, Astrid Olivia Leech

Education and Research Centre Smurfit Building, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland


Background: Junctional Adhesion Molecule-A (JAM-A) has important physiological functions in epithelial and endothelial barriers, but its overexpression has also been linked with tumour progression and poor prognosis in various malignancies. Since JAM-A can be enzymatically cleaved (“cJAM-A”) and has been detected in the bloodstream, we hypothesized that cJAM-A shed from tumours overexpressing JAM-A may represent a possible predictor of treatment resistance in breast cancer.

Methods: An assay was optimised to detect cJAM-A in serum/plasma. Samples were obtained from HER2-positive breast cancer patients (n=20) in Beaumont Hospital. Independently, serial samples were obtained from a diverse international cohort of breast cancer patients (n=53). Separately, a semi-in vivo chick embryo xenograft model was used to evaluate a novel potential role for JAM-A overexpression and cleavage in driving tumour progression.

Results: Serum cJAM-A levels in therapy-resistant patients was significantly higher than those in treatment-sensitive patients (P<0.05) in an Irish cohort. Semi-in vivo work showed a macroscopic increase in tumour growth in xenograft tumours either over-expressing JAM-A or treated with cleaved JAM-A. Correspondingly, pharmacological inhibition of JAM-A cleavage reduced gross tumour size and histological evidence of tumour invasiveness.

Conclusions: Our data suggest that cJAM-A merits further investigation as a novel biomarker enabling prospective identification of patients at greatest risk of developing therapeutic resistance. We are in the process of expanding this work in a large cohort of serially-sampled breast cancer patients from an international site.

Keywords: Adhesion molecules; biomarkers; breast cancer; xenograft


doi: 10.21037/map.2020.AB141
Cite this abstract as: Rutherford EJ, Richards C, Konrad Hill AD, Hopkins A, Leech AO. Novel clinical roles for junctional adhesion molecule—a in breast cancer progression. Mesentery Peritoneum 2020;4:AB141.