Prostaglandin F2α stimulates motility and invasion in colorectal tumor cells

Autor: Abderrahmane Kaidi, SD Chell, Henry N. Jabbour, Ann C. Williams, Christos Paraskeva, David Qualtrough
Rok vydání: 2007
Předmět:
Zdroj: International Journal of Cancer. 121:734-740
ISSN: 1097-0215
0020-7136
Popis: Colorectal cancer remains a major cause of cancer deaths globally. The inducible form of cyclooxygenase (COX-2), the key enzyme in prostanoid biosynthesis, is overexpressed in over 80% of colorectal cancers.1 Furthermore, COX-2 is frequently expressed during the premalignant adenoma stages of colorectal tumorigenesis and shows a size dependent increase in expression indicating a role in tumor progression.2 The importance of COX-2 expression in colorectal tumor progression has been highlighted by studies both in vitro and in vivo, and its effects are mediated through its prostanoid products.3 COX-2 catalyses the formation of prostaglandin H2 (PGH2) from arachidonic acid and PGH2 is subsequently converted to several structurally related primary prostanoids, namely prostaglandin E2 (PGE2), PGD2, PGI2, Thromboxane A2 and prostaglandin F2α (PGF2α) by the action of specific synthases. Increased levels of PGE2 have been observed in colorectal cancers when compared with histologically normal tissue.4-6 Subsequent studies using in vitro models have shown that PGE2 is able to promote tumor cell growth,7,8 modulate apoptosis9 and increase cell motility.8 COX-2 expression and subsequent PGE2 production has also been shown to enhance the production of angiogenic factors.10-12 Studies of prostaglandin production in colorectal tumors have also identified the production of other primary prostanoids including PGF2α.4-6 In 1 study on intestinal tissue from familial adenomatous polyposis (FAP) patients, the detected levels of PGF2α were 30-fold higher than for PGE2.13 Although widely studied in other tissues, the potential role of PGF2α in colorectal cancer remains to be elucidated. The most extensively studied area of PGF2α biology is its role in the regression of the corpus luteum during pregnancy.14 Interestingly, PGF2α stimulates the proliferation of Swiss mouse 3T3 cells with greater efficacy than PGE2.15,16 PGF2α is thought to largely act through the FP G-protein-coupled receptor, although the expression of this receptor has not been determined in colorectal cancer. Because of the importance of COX-2 overexpression, the aim of the study presented here was to investigate the potential role of PGF2α in colorectal tumorigenesis. To this end, we determined the expression of the FP receptor in normal and neoplastic colorectal tissue, and a panel of adenoma and carcinoma-derived cell lines. The production of PGF2α was examined in parallel with that of PGE2 in the cell lines. Finally, we assessed the ability of both PGF2α and PGE2 to promote cell motility and invasion which represent important hallmarks of malignant progression in these tumors.
Databáze: OpenAIRE
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