Prostaglandin F(2alpha) stimulates motility and invasion in colorectal tumor cells.
Increased expression of cyclooxygenase-2 (COX-2) and subsequent prostaglandin production is an important event in several human malignancies, including colorectal cancer. COX-2 mediated prostanoid synthesis has been shown to play a key role in tumor progression with prostaglandin E(2) (PGE(2)) being shown to promote tumor growth, invasion and angiogenesis. The role of the other prostaglandins produced by COX-2 in tumors remains poorly understood. We have shown that colorectal tumor cells produce prostaglandin F(2alpha) (PGF(2alpha)) and provide evidence that PGF(2alpha) may play an important role in colorectal tumorigenesis. Our data show that PGF(2alpha) is secreted by both colorectal adenoma and carcinoma-derived cell lines at levels in excess of those detected for PGE(2). These cell lines were also found to express the PGF(2alpha) receptor (FP) indicating potential autocrine effects of PGF(2alpha). This finding is further supported by an in vivo immunohistochemical study of FP expression in resected colon tissue. These data show epithelial expression of FP in normal colorectal mucosa and also in colorectal adenomas and carcinomas. We compared the relative abilities of PGF(2alpha) and PGE(2) to induce cell motility in vitro in colorectal tumor cell lines and show the first evidence of prostaglandin-induced cell motility in colorectal adenoma cell lines. PGF(2alpha) induced cell motility with equivalent potency to PGE(2) in all the cell lines tested and was also shown to increase the invasion of carcinoma-derived cells into reconstituted basement membrane. These data show that PGF(2alpha) may play an important role in the malignant progression of colorectal tumors.
Qualtrough
David
D
Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom. david.qualtrough@bristol.ac.uk
Kaidi
Abderrahmane
A
Chell
Simon
S
Jabbour
Henry N
HN
Williams
Ann C
AC
Paraskeva
Christos
C
D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015237:Dinoprost / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness
D015237:Dinoprost; D015232:Dinoprostone