Qualtrough David, Kaidi Abderrahmane, Chell Simon, Jabbour Henry N, Williams Ann C, Paraskeva Christos
Cancer Research UK Colorectal Tumour Biology Research Group, Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom.
Int J Cancer. 2007 Aug 15;121(4):734-40. doi: 10.1002/ijc.22755.
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.
环氧化酶-2（COX-2）表达增加及随后的前列腺素生成是包括结直肠癌在内的多种人类恶性肿瘤中的一个重要事件。COX-2介导的前列腺素合成已被证明在肿瘤进展中起关键作用，前列腺素E2（PGE2）可促进肿瘤生长、侵袭和血管生成。COX-2产生的其他前列腺素在肿瘤中的作用仍知之甚少。我们已表明结直肠肿瘤细胞可产生前列腺素F2α（PGF2α），并提供证据表明PGF2α可能在结直肠癌发生中起重要作用。我们的数据显示，结直肠腺瘤和癌衍生细胞系分泌的PGF2α水平超过检测到的PGE2水平。还发现这些细胞系表达PGF2α受体（FP），表明PGF2α可能具有自分泌作用。对切除的结肠组织中FP表达的体内免疫组化研究进一步支持了这一发现。这些数据显示FP在正常结直肠黏膜以及结直肠腺瘤和癌中均有上皮表达。我们比较了PGF2α和PGE2在体外诱导结直肠肿瘤细胞系细胞运动的相对能力，并首次证明了前列腺素诱导结直肠腺瘤细胞系细胞运动。在所有测试的细胞系中，PGF2α诱导细胞运动的效力与PGE2相当，并且还显示可增加癌衍生细胞对重组基底膜的侵袭。这些数据表明PGF2α可能在结直肠肿瘤的恶性进展中起重要作用。
