Poster Presentation COSA-IPOS Joint Scientific Meeting 2012

Mechanism of IGF induced epithelial-to-mesenchymal transition (EMT) in melanoma progression (#714)

Prashanth Prithviraj 1 , Aparna Jayachandran 1 , Matthew Anaka 1 , Jonathon Cebon 1
  1. LUDWIG INSTITUTE FOR CANCER RESEARCH, HEIDELBERG HEIGHTS, VIC, Australia

Background: Melanoma is a common and highly aggressive form of skin cancer with a high propensity to metastasise. Despite recent improvements in treatment, metastatic melanoma is nearly always fatal. The role of EMT in facilitating cancer metastasis, progression and recurrence in various cancers has been demonstrated1,2. Growing evidence supports the role of EMT in melanoma progression3,4. However, detailed mechanistic insights into how EMT impacts metastasis in melanoma are currently lacking.

Rationale: Since IGF signalling is elevated in invasive melanoma cells and has been implicated in promoting EMT in other cancers, it is conceivable that IGF may contribute to EMT in melanoma. The aim of this study is to identify and target key components of the IGF signaling pathway to inhibit or reverse the EMT process in melanoma cells.

Methods & Results: Microarray analysis identified components of IGF signalling pathway that are differentially expressed. Using qPCR, we confirmed differential expression of various components of IGF signalling pathway in invasive melanoma cell lines. We tested the influence of IGF ligands on the proliferative abilities of melanoma cells by MTS assay. Furthermore, we tested the invasive and migratory behaviour of melanoma cells post IGF treatment by subjecting them to Matrigel coated or uncoated Boyden chambers. We studied the effect of IGF treatment on the expression of classical EMT markers.

Conclusion: Our results demonstrate that IGF signalling plays a critical role in melanoma progression by facilitating EMT. We suggest targeting IGF signalling as a promising strategy to limit melanoma progression.

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  2. Graham, T. R., H. E. Zhau, et al. (2008). "Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells." Cancer Res 68(7): 2479-2488.
  3. Mikesh LM, Kumar M, Erdag G, Hogan KT, Molhoek KR, May MW, Slingluff CL Jr. Evaluation of molecular markers of mesenchymal phenotype in melanoma. Melanoma Res. 2010 Dec;20(6):485-95
  4. Kudo-Saito C, Shirako H, Takeuchi T, Kawakami Y. Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell. 2009 Mar 3; 15(3): 195-206