Possible relationship between glycosphingolipids and the formation of metastasis in certain human experimental tumors.
Two tumors, human sarcoma #1 (HS #1) and human epidermoid carcinoma #3 (HEp #3), were cultured on the chorioallantoic membrane of chick embryos. Under experimental conditions, HS #1 does not metastasize, whereas HEp #3 metastasizes extensively to chick embryo lungs and other organs. The glycosphingolipid profiles of these tumors were studied and HEp #3 wad found to contain about 2.5-fold less lipid-bound sialic acid per 100 mg of total lipid extracted than did HS #1, due mainly to smaller levels of monosialoganglioside (3.7-fold) and disialoganglioside (3.8-fold) in HEp #3. The total amount of neutral glycosphingolipids was approximately the same in both tumors, but their profiles differed. Treatment of these tumors with 6,7,8,9-tetrahydro-1-mercapto-1,2,4-triazolo-[4,3-a]quinazolin-5-ol (2.5 mg/egg/tumor) completely inhibited the formation of metastases in HEp #3 and increased the total content of lipid-bound sialic acid in the tumor by 63% (hematoside, monosialoganglioside, and disialoganglioside by 71, 99, and 67%, respectively). No change was seen in the content of lipid-bound sialic acid in HS #1. Treatment of HEp #3 with a smaller dose of te quinazolinol derivative (1.25 mg/egg) caused an average of 88% inhibition of metastasis, with a 37% increase in  lipid-bound sialic acid. Another compound, 2,5-diphenylthiazolo-[5,4-d]thiazole (500 microgram/egg), completely inhibited the formation of metastasis and caused a substantial increase in the amount of lipid-bound sialic acid (77%). The data showed the existence of a correlation between the level of gangliosides in HEp #3 and the ability of these tumors to metastasize.
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002642:Chick Embryo; D005732:Gangliosides / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology; D013844:Thiazoles / Q000494:pharmacology
D005732:Gangliosides; D006028:Glycosphingolipids; D011799:Quinazolines; D013844:Thiazoles