title: Fatty acid modulation of tumor cell adhesion to microvessel endothelium and experimental metastasis.
abstract: Tumor cell interaction with the endothelium of the vessel wall is a rate limiting step in metastasis. The fatty acid modulation of this interaction was investigated in low (LM) and high (HM) metastatic B16 amelanotic melanoma (B16a) cells. 12(S)-HETE increased the adhesion of LM cells to endothelium derived from pulmonary microvessels. All other monohydroxy and dihydroxy fatty acids were ineffective. LTB4 induced a modest stimulation but LTC4, LTD4, LTE4 as well as LXA4 and LXB4 were ineffective. The 12(S)-HETE enhanced adhesion of B16a cells was inhibited by pretreatment with 13(S)-HODE but not by 13(R)-, 9(S)-HODE or 13-OXO-ODE. 13(S)-HODE decreased adhesion of HM B16a cells to endothelium. 12(S)-HETE enhanced surface expression of integrin alpha IIb beta 3 and monoclonal antibodies against this integrin but not against alpha 5 beta 1, blocked enhanced but not basal adhesion to endothelium. Intravenous injection of 12(S)-HETE treated LM cells resulted in increased lung colonization (experimental metastasis). This effect was specific for 12(S)-HETE and was inhibited by 13(S)-HODE but not by other HODE's. 12(S)-HETE also enhanced lung colonization by HM cells and 13(S)-HODE decreased lung colonization by HM cells. Our results suggest a highly specific bidirectional modulation of metastatic phenotype and lung colonization by 12(S)-HETE and 13(S)-HODE.
authors: Department of Radiation Oncology, Wayne State University, Detroit, MI 48202.
authors: K V
authors: KV
authors: Honn
authors: K K
authors: KK
authors: Nelson
authors: C
authors: C
authors: Renaud
authors: R
authors: R
authors: Bazaz
authors: C A
authors: CA
authors: Diglio
authors: J
authors: J
authors: Timar
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015777:Eicosanoids / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D016023:Integrins / Q000378:metabolism; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
chemical_list: D015777:Eicosanoids; D016023:Integrins