PREPARATION AND CHARACTERIZATION OF DIFFERENTLY AGGREGATED COLORECTAL-CARCINOMA CELL SUBPOPULATIONS FROM SURGICAL SPECIMENS

The loss of intercellular adhesion within the primary tumor is one of the key events leading to metastasis. Although a number of adhesion mo lecules involved in intercellular adhesion have been described in expe rimental systems, the clinical relevance of many of these molecules st ill has to be determined, We tried to assess the contribution of membr ane-bound carbohydrates and of E-Cadherin, CEA, and Sia-LeA for interc ellular adhesion of cells isolated from colorectal carcinoma tissue di rectly obtained from the surgeon. A subpopulation of nonaggregating ce lls was prepared by means of slowly passing of freshly isolated cells through a series of sieves with decreasing mesh widths. Nonaggregating cells differed mainly in two aspects from aggregated cells: (i) deter mination of lectin binding and of specific sialytransferase activities revealed enhanced alpha 2,6-sialylation of nonaggregating cells, and (ii) staining with specific antibodies documented a loss of E-Cadherin reactivity of such cells. An enhanced activity of beta-galactoside al pha 2,6-sialytransferase (ST6Gal 1) was found in metastasizing colorec tal carcinomas; however, its biological function has to be shown. Our results suggest that ST6Gal 1 is responsible for reduced homotypic agg regation of colorectal carcinoma cells and may thus facilitate the rel ease of single cells from the primary tumor.