Investigating the role of TFF1 in Mammary and Prostate Carcinoma

Abstract

Trefoil Factor-1 (TFF1) belongs to the family of trefoil factor peptides. Trefoil factors protect the gastrointestinal tract against mucosal injury. Trefoil peptides are upregulated and secreted in an autocrine and paracrine fashion in response to gastrointestinal injury. They facilitate cell migration and prevent anoikis. TFF1 is also expressed in various tissues and regulated by multiple cellular processes. Several studies have also demonstrated increased expression of TFF1 in a high percentage of mammary and prostate carcinoma cases. However, the functional role of autocrine TFF1 in mammary and prostate carcinoma has not been previously elucidated. Herein, I demonstrate that forced expression of TFF1 in mammary carcinoma cells resulted in increased total cell number as a consequence of increased cell proliferation and survival. Forced expression of TFF1 enhanced anchorage-independent growth and promoted scattered cell morphology with increased cell migration and invasion. Moreover, forced expression of TFF1 increased tumor size in xenograft models. Conversely, depletion of TFF1 by RNA interference (RNAi) in mammary carcinoma cells significantly reduced anchorageindependent growth and migration. Furthermore, neutralization of secreted TFF1 protein by polyclonal antibody decreased mammary carcinoma cell viability in vitro and resulted in regression of mammary carcinoma xenografts. In prostate carcinoma cell lines utilized herein, I demonstrate that forced expression of TFF1 did not affect proliferation and anchorage-independent growth. However, forced expression of TFF1 enhanced prostate carcinoma cell migration and invasion. Additionally, functional inhibition of TFF1 by RNAi or polyclonal antibody abrogated prostate carcinoma cell invasion. I have therefore demonstrated that TFF1 possesses oncogenic functions in mammary carcinoma cells and enhances prostate carcinoma cell invasion. Functional antagonism of TFF1 can therefore be considered as a novel therapeutic strategy for mammary carcinoma.