Multiple use of a signal transduction pathway in tumor cell invasion.
Recent reports have indicated that a poorly characterized signaling pathway involving 12-lipoxygenase and PKC is involved in several steps of the metastatic cascade such as tumor cell adhesion to matrix, lysosomal enzyme release and migration. We investigated here the upstream elements of this signalling pathway looking for receptors which it might be coupled to. We described tumor cell alpha IIb beta 3-like integrin and the AMF receptor, gp78, as two transmembrane receptors which utilize the 12-lipoxygenase/PKC signaling. Furthermore, we compared the in vivo expression of the signal components of the "autocrine motility cycle" (gp78, 12-LOX and PKCa-Tímár et al 1993) in human prostate carcinoma cell lines (PC3 and DU145) with different invasive potential. We report here that all three components of this cycle are overexpressed three fold in vivo in the more aggressive tumor, suggesting that this signalling pathway might regulate the invasive phenotype-at least in the studied tumor cells.
Tímár
J
J
1st Institute of Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Budapest, Hungary. jtimar@korb1.sote.hu
Rásó
E
E
Fazakas
Z S
ZS
Silletti
S
S
Raz
A
A
Honn
K V
KV
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D005956:Glucose-6-Phosphate Isomerase / Q000494:pharmacology; D006801:Humans; D039661:Integrin beta3; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D015703:Antigens, CD; D039661:Integrin beta3; D009363:Neoplasm Proteins; D010980:Platelet Membrane Glycoproteins; D018121:Receptors, Cytokine; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; C555000:AMFR protein, human; C555002:Amfr protein, mouse; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D011493:Protein Kinase C; D005956:Glucose-6-Phosphate Isomerase