Trefoil factor family-3 is associated with aggressive behavior of colon cancer cells.
OBJECTIVE
Trefoil factor family 3 (TFF3) is expressed by intestinal epithelial cells and it mainly functions to protect the mucosa from injury. Expression of TFF3 has been correlated with a poor prognosis in patients with cancer, but little is known about whether TFF3 directly contributes to the malignant behavior of cancer cells. The present study was conducted to determine whether TFF3 expression contributes to the malignant behavior of cancer cells in vitro and in vivo.


METHODS
Two subclones of a metastatic rat colorectal cancer cell line, demonstrated previously to manifest aggressive (LN cells) and non-aggressive (LP cells) growth in vivo, were analyzed for expression of TFF3 and tested in assays of cancer cell migration, invasion, and apoptosis in vitro, and mortality in vivo.


RESULTS
The aggressive LN cell line endogenously expressed TFF3 and supported the transcription of a TFF3 promoter-driven reporter construct, whereas the non-aggressive LP cell line did not express TFF3. LN cells demonstrated enhanced migration, invasion, and less apoptosis compared to LP cells. Transfecting TFF3 into LP cells enhanced their ability to migrate, invade, block apoptosis, and behave more aggressively in vivo, thereby resembling the phenotype of LN cells.


CONCLUSIONS
In rat colon cancer cells, both endogenous and constitutive expression of TFF3 correlates with an aggressive phenotype. These data provide direct evidence that TFF3 contributes to the malignant behavior of cancer cells.
Yio
Xianyang
X
The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Zhang
Jie-yu
JY
Babyatsky
Mark
M
Chen
Anli
A
Lin
Jing
J
Fan
Qui-Xiang
QX
Werther
J Lawrence
JL
Itzkowitz
Steven
S
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000473:pathology* / Q000662:veterinary; D020869:Gene Expression Profiling; D009361:Neoplasm Invasiveness; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D011379:Prognosis; D051381:Rats; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured
D009479:Neuropeptides; C099037:TFF3 protein, rat; D000071165:Trefoil Factor-3