lysophosphatidylserine and Colorectal-Neoplasms

Although lysophospholipids are known to play an important role in the development and progression of several kinds of cancers, their role in human colorectal cancer is as yet unclear. In this study, we aim to investigate lysophospholipid levels in colorectal cancer tissues to identify lysophospholipids, the levels of which change specifically in colorectal cancers. We used liquid chromatography-tandem mass spectrometry to measure lysophospholipid levels in cancerous and normal tissues from 11 surgical specimens of sigmoid colon cancers, since recent advances in this field have improved detection sensitivities for lysophospholipids. Our results indicate that, in colon cancer tissues, levels of lysophosphatidylinositol and lysophosphatidylserine were significantly higher ( p = 0.025 and p = 0.01, respectively), whereas levels of lysophosphatidic acid were significantly lower ( p = 0.0019) than in normal tissues. Although levels of lysophosphatidylglycerol were higher in colon cancer tissues than in normal tissues, this difference was not found to be significant ( p = 0.11). Fatty acid analysis further showed that 18:0 lysophosphatidylinositol and 18:0 lysophosphatidylserine were the predominant species of lysophospholipids in colon cancer tissues. These components may be potentially involved in colorectal carcinogenesis.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Lysophospholipids; Male; Middle Aged; Prognosis

Lysophosphatidylserine (lysoPS) is a type of lysophospholipid mediator, which is involved in allergic conditions and tumor progression. We investigated the physiological function of lysoPS on colorectal cancer (CRC) cell lines, as well as the involved receptor and signaling pathways.. Expression of lysoPS receptors on six cell lines was examined by reverse transcription-polymerase chain reaction (RT-PCR). The physiological functions of lysoPS were investigated, and experiments using small interfering RNA (siRNA) or inhibitors of the signaling pathways were conducted.. Among the three lysoPS receptors, GPR34 was highly expressed on all cell lines. LysoPS stimulated the chemotactic migratory ability. Wortmannin inhibited the migratory ability, as well as the GPR34 knock-down, strongly suggestive of the involvement of this receptor in the PI3K/Akt pathway.. The involved receptor and pathways in the migratory ability in response to lysoPS was demonstrated, which opens premises for targeting as a new strategy for prevention and treatment of colorectal cancer.

Topics: Cell Adhesion; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Extracellular Matrix Proteins; Gene Knockdown Techniques; Humans; Lysophospholipids; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, Lysophospholipid; Signal Transduction