67P - TGF-β2, a novel target of CD44-promoted breast cancer invasion

Date 08 May 2014
Event IMPAKT 2014
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Hamad Al-Riyami
Citation Annals of Oncology (2014) 25 (suppl_1): i23-i24. 10.1093/annonc/mdu070
Authors H. Al-Riyami1, I. Gupta1, S. Madani1, S. Shanmuganathan1, M. E Abdraboh1, Y. Al-Farsi2, M. Raj1, A. Ouhtit1
  • 1Department Of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khoud - Muscat/OM
  • 2Department Of Family Health And Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khoud - Muscat/OM


Hyaluronan (HA) mediates communication between cancer cells and the environment via interactions with the cell surface receptor CD44. We have previously shown that CD44-HA interaction in BC cells promotes adhesion to bone marrow endothelial cells. This suggests that HA/CD44 signalling may be correlated with breast cancer (BC) metastasis. The long-term objective of this study is to increase our understanding of the mechanisms by which CD44-HA interaction promotes BC metastasis, and further identify and validate CD44-downstream transcriptional targets for anti-metastatic therapy. Pursuant to this goal, we have developed a tetracycline (tet)-regulated expression of CD44 gene in the BC cell line MCF-7 (B5 clone) and identified TGF-beta2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44s-downstream transcriptional target by microarray analysis. To further validate this finding, the same RNA samples, used for microarray analysis and their corresponding protein lysates collected from the BC cell line MCF-7-B5, were examined for CD44 expression in the presence of HA for 18, 24, and 48hr post-tet withdrawal. Expression of TGF-beta 2 was examined using RT-PCR and western-Blot analyses. Our results showed that TGF-beta2 mRNA levels were significantly elevated following the removal of tet at 18, 24, and 48h post-HA stimulation compared to the parental cells. Furthermore, the TGF-beta2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tet. More interestingly, inhibition of CD44 gene by RNAi method decreased TGF-beta2 expression upon HA-stimulation and in the absence of tet. Our data strongly support the hypothesis that TGF-beta2 is a potential target of HA/CD44- downstream-signaling mediating BC cell invasion. Ongoing investigation aims to elucidate the signal transduction pathways coupling CD44 to the regulation of TGF-beta2 expression, and further validate CD44/TGF-beta2 axes in breast tumor invasion and metastasis.


All authors have declared no conflicts of interest.