Platelet-activating factor and human thyroid cancer

Abstract

Objective: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator involved in several types of cancer in humans. The levels of PAF, lyso-PAF (the PAF precursor), phospholipase A 2 activity (PLA 2 , the enzymatic activity implicated in lyso-PAF formation) and acetylhydrolase activity (AHA, the PAF-degrading enzyme) were investigated in various diseased thyroid tissues. Subjects: Control and diseased tissue of patients with a hyperplastic goitre (n ¼ 14), a benign adenoma (n ¼ 12) and a papillary thyroid carcinoma (n ¼ 15) were investigated. Results: PAF receptor transcripts were found in the human thyroid tissue. PAF, lyso-PAF, PLA 2 and AHA were present in control thyroid tissues, their levels being significantly correlated with each other, suggesting tiny regulations of the PAF metabolic pathways inside the thyroid gland. PAF, lyso-PAF, PLA 2 and AHA levels remained unchanged in diseased tissues of patients with a hyperplastic goitre, a benign adenoma and a papillary thyroid carcinoma. No difference was found between PAF, lyso-PAF, PLA 2 and AHA levels with respect to the TNM tumour status and the histological subtype of papillary thyroid carcinoma. No correlation was found between tissue PAF levels and those of vascular endothelial growth factor and basic fibroblast growth factor, two angiogenic growth factors involved in thyroid cancer and that mediate their effect through PAF release in breast and colorectal cancer. Conclusion: PAF, PAF receptor transcripts and the enzymatic activities implicated in PAF production and degradation are present in the thyroid gland. While the physiological role of PAF is presently unknown in thyroid physiology, this study highlights no evidence for a potentially important role of PAF during human thyroid cancer, a result that markedly differs from breast and colorectal ones.European Journal of Endocrinology 153 31-40

Inflammation and melanoma growth and metastasis: The role of platelet-activating factor (PAF) and its receptor

“…Higher amounts of PAF and PAFR transcripts 1 and 2 were found in hepatocellular carcinoma specimens as compared with non-tumor tissues, while no difference was observed in PLA 2 , lyso-PAF and PAF-AH levels [99]. No changes in the levels of these molecules were detected in papillary thyroid cancer [100]. PAFR transcripts as well as PAF, PLA 2 and PAF-AH were detected in human meningiomas, although no correlation was observed between their levels and tumor grade or tumor vascularization [101].…”

“…A complex approach involving simultaneous detection of PAF, PAF precursor lyso-PAF, PAFR, PAF-AH and PLA 2 transcripts was used to examine the role of this pathway in the progression of tumors of different origins [96][97][98][99][100][101][102]. In colon cancer patients' blood, levels of both PAF-AH and PLA 2 were found to be elevated as compared to those in healthy individuals, while no difference was found in PAF levels in the plasma [96].…”

Mechanisms linking obesity and cancer

“…PAF activity has been implicated in several cancers, including thyroid [56] and breast [57] cancers. PAF promotes proliferation, migration, and angiogenesis in human breast cancer cells [57].…”

Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF)

“…The practical outcome of these possibilities in our context is that the overall growth rate of a tumor cell in the PAFR-KO mice could depend more on the tumor's response to PAF than on that of the host. For instance, some myeloid leukemic cells do not express receptors for PAF (Berdel et al, 2005) and samples of human thyroid cancers show normal levels of PAF and related enzymes (Denizot et al, 2005). In our present work, the marked stimulation of the Ehrlich tumor but not of the Colon 26 tumor could reflect such a differential sensitivity to PAF in the two tumor cell lines.…”