title: Regulation of carcinoembryonic antigen release from colorectal cancer cells.
abstract: Clinical and experimental evidence suggest that circulating carcinoembryonic antigen (CEA) released from tumor cells has an instrumental role in colorectal cancer-liver metastasis. However, the precise mechanism of the regulation of the CEA release from cancer cells is not known. We investigated if the rate of CEA and another GPI-anchored protein, alkaline phosphatase (AP) release is correlated with cellular glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) expression. We also evaluated the effects of phosphatidic acid (PA), a compound known to inhibit GPI-PLD activity, on the CEA and AP release from colon cancer cells. The expression of CEA, GPI-PLD, and AP in five colon carcinoma cells (LS180, Caco2, SW742, SW1116, and HT29/219) was verified by immunoblot and real-time RT-PCR analysis. The amounts of CEA and AP released into cell culture media were determined using ELISA and a colorimetric assay, respectively. We examined the effects of PA (20-100 μM) on CEA and AP release from LS180 cells. All five cancer cell lines analyzed expressed GPI-PLD protein. While there was a positive relationship between AP release and the levels of GPI-PLD transcript expression, we found no direct correlation between CEA released from cancer cells and the GPI-PLD mRNA expression level. However, the rate of CEA release was positively associated with the level of CEA transcript expression. In comparison to controls, the release of GPI-anchored CEA and AP, but not CA19-9 was inhibited significantly by both crude and pure phosphatidic acid (by 56 and 54.5%, respectively). Using PA for inhibiting CEA release from cancer cells may have therapeutic application in preventing CRC-liver metastasis.
authors: Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Zand Street, Shiraz, Fars, Iran.
authors: Abbas
authors: A
authors: Pakdel
authors: Fakhraddin
authors: F
authors: Naghibalhossaini
authors: Pooneh
authors: P
authors: Mokarram
authors: Mansooreh
authors: M
authors: Jaberipour
authors: Ahmad
authors: A
authors: Hosseini
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D010712:Phosphatidic Acids / Q000494:pharmacology; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002272:Carcinoembryonic Antigen; D003470:Culture Media; D010712:Phosphatidic Acids; D012333:RNA, Messenger; D000469:Alkaline Phosphatase; D010739:Phospholipase D; C065017:glycoprotein phospholipase D