Differential expression of adhesion molecules (CD44, ICAM-1 and LFA-3) in cancer cells crown in monolayer or as multicellular spheroids

Multicellular tumor spheroids have been used to examine numerous aspects of tumor biology since they often recreate the in vivo tumor environment much more closely than other models. Since the three-dimensional organization of cancer cells into spheroids is based upon cell-cell interactions which appear dramatically different in spheroids with respect to monolayer cultures, it can be hypothesized that a modulation in the expression of the molecules which are directly responsible for cell-cell and cell-matrix interactions, particularly the cell adhesion molecules (CAMs), may be involved. In order to test this postulate, the expression of three important CAMs involved in tumor processes (CD44, ICAM-1 and LFA-3) in the human cancer cell lines HT29 (colon adenocarcinoma), A431 (squamous epidermal carcinoma) and A2780 (ovarian carcinoma) grown in monolayer or as multicellular spheroids was compared. The results demonstrate that only two of the lines (HT29 and A431) formed spheroids after six days of gyratory culture while A2780 cells did not form such structures after up to 8 days of culture. In the two cell lines which did form early phase multicellular spheroids, flow cytometric analysis revealed that important differences exist between the same cells grown in monolayer and as spheroids in the quantity of expression of CAMs.