Trefoil factor-3 expression in human colon cancer liver metastasis

Abstract

Deaths from colorectal cancer are often due to liver metastasis. Trefoil factor-3 (TFF3) is expressed by normal intestinal epithelial cells and its expression is maintained throughout the colon adenoma-carcinoma sequence. Our previous work demonstrated a correlation between TFF3 expression and metastatic potential in an animal model of colon cancer. The aim of this study was to determine whether TFF3 is expressed in human colon cancer liver metastasis (CCLM) and whether inhibiting TFF3 expression in colon cancer cells would alter their invasive potential in vitro. Human CCLMs were analyzed at the mRNA and protein level for TFF3 expression. Two highly metastatic rat colon cancer cell lines that either natively express TFF3 (LN cells) or were transfected with TFF3 (LPCRI-2 cells), were treated with two rat TFF3 siRNA constructs (si78 and si365), and analyzed in an in vitro invasion assay. At the mRNA and protein level, TFF3 was expressed in 17/17 (100%) CCLMs and 10/11 (91%) primary colon cancers, but not in normal liver tissue. By real time PCR, TFF3 expression was markedly inhibited by both siRNA constructs in LN and LPCRI-2 cells. The si365 and si78 constructs inhibited invasion by 44% and 53%, respectively, in LN cells, and by 74% and 50%, respectively, in LPCRI-2 cells. These results provide further evidence that TFF3 contributes to the malignant behavior of colon cancer cells. These observations may have relevance for designing new diagnostic and treatment approaches to colorectal cancer.

Aberrant expression of trefoil factor 3 is associated with colorectal carcinoma metastasis

“…[15] A study revealed that TFF3 was expressed in 100% colonic cancer liver metastasis and in 91% of primary colon cancers at the mRNA and protein level. [21] These data provide direct evidences that TFF3 contributes to the malignant behavior of colonic cancer cells. Abnormal expression of TFF3 has been reported in various human solid tumors, such as breast, prostate, lung and gastric cancer, and elevated expression of TFF3 in these cancers usually indicate poor outcome.…”

Microarray Analysis Reveals Distinct Gene Expression Profiles Among Different Tumor Histology, Stage and Disease Outcomes in Endometrial Adenocarcinoma

“…The EphA1receptor/ephrin ligand system has been implicated in tumor progression in a number of malignancies where they are strongly involved in tumorigenesis including metastatsis, angiogenesis and invasion [11], [18]–[20]. Trefoil factor 3 (TFF3) , located at 21q22.3, belongs to a family of small mucin-associated polypeptides that can regulate cancer progression by increasing tumor metastasis [16], [17], [21], [22]. E74-like factor 5 (ELF5) or epithelium –specific ETS factor 2 (ESE2) , located at 11p15-p13, is a member of the ETS family of transcription factors and has been implicated to play a key role in cell proliferation, differentiation, apoptosis and tumorigenesis [17], [23].…”

Inhibition of ErbB-2 induces TFF3 downregulation in breast cancer cell lines

“…TFF3 is overexpressed in a variety of human malignancies including mammary (12), gastric (13,14), prostate (15), hepatocellular (16), and endometrial (17) carcinomas. It has demonstrated prosurvival, proinvasive, and proangiogenic activities in cells derived from several common human solid tumors (18)(19)(20)(21)(22)(23). Although the role of TFF3 in mammary carcinoma remains undefined, the prognostic or predictive value of TFF3 expression in mammary carcinoma has been indicated by several clinical studies.…”