Fgf10: type iii epithelial mesenchymal transition and invasion in breast cancer cell lines

Ali Kian saei,1,* Gholam reza riazi,2 Ebrahim azizi,3 Saeid amanpour,4 Samad muhammadnehad,5

Abstract


Introduction

Metastasis is one of the important characteristics of a cancer cell. the process called epithelial mesenchymal transition (emt) is a known process related to the initiation of cell migration and metastasis. finding a way to regulate this phenomenon will have a practical importance for clinical outcome of cancer in life span and quality. emt categorized into three types: type 1 in gastrulation, type 2 in wound healing and type 3 in metastasis. because of some similarities between cellular and molecular procedures during gestational life and cancer, investigations about the possible role of dysregulated molecules, which are responsible for organogenesis and rapid growth of cells in the fetus, on invasion and cancer metastasis is very important. fibroblastic growth factor-10 (fgf-10) is a well-known protein in type i emt and organogenesis. there are some evidences showing that in some cancers, such as prostate cancer, there are correlations between the expressing levels of fgf-10and invasion of cancer cells. hence, this study set out to show that the effect of these cell-line behaviors is directly related to fgf-10 through regulation of emt mechanisms in which various types of signaling pathways are involved.

Methods

Cell lines and primers, gene regulation by sirna and recombinant protein, western blot analysis, fluorescent microscopy, mtt assay, colony agar assay, migration assay, wound healing assay, apoptosis (hoechst acrydine orange), real time pcr.

Results

Positive effect of fgf-10 on proliferation. tumorgenesis is increased under fgf-10 effect. fgf-10 induces and increases wound healing ability of cells. invasion and migration ability of cells dependents on fgf-10 production. apoptosis is decreased under fgf-10 protein. emt induction factors change under fgf-10 effects and initiate emt program. fgf-10 induced gsk3β phosphorylation in breast cancer cells.

Conclusion

Our data suggested that if fgf-10, a protein with function in early life organogenesis and developmental roles, is dysregulated in cancer, it can act as a wild agent involving cell proliferation, immortality, and tumorigenesis, plus emt followed by invasion and metastasis.

Keywords

The important role of fgf-10 in type iii emt on cancer cells and initiation of metastasis via variou