Abstract:

Tumor microenvironments cause a wide range of responses in both cancer cells and surrounding host cells, inducing gene expressions of growth factors and their receptors to lead such as angiogenesis and changes of metabolic switch. To examine the possible mechanism by which cancer cells increase growth and survival during tumor progression, we used human squamous cell carcinoma derived cell line DJM1 as a malignant tumor model. Here we report that the cancer cells in the avasculature area in the mouse xenografts were able to induce the expression of fibroblast growth factor receptor 3 (FGFR3) known as an oncogene. In vitro experiments confirmed that serum-starvation induced the marked increased expression of FGFR3 in DJM1 cells. As a significant finding, two alternatively spliced isoforms of FGFR3, FGFR3IIIb and FGFR3IIIc, expressed in normal epithelial cells or in mesenchymal cells respectively, were both increased in DJM1 cells under the serum-starved conditions. Moreover, ectopic expression of FGFR3IIIc in DJM1 cells in vitro greatly enhanced anchorage-dependent and -independent growth in response to FGF2, suggesting that dysregulation of FGFR3 expression has a role in tumor growth and survival in vivo. These findings provide an insight into the mechanism of FGFR3-dependent tumor progression and a basis for the development of cancer therapies.