N-linked oligosaccharides and metastatic propensity in in vivo selected mouse mammary adenocarcinoma cells

Studies using metastatic variant selected in vivo from a cloned parental cell line demonstrate that the expression of β1-6 branched, N-linked carbohydrates and sialic acid were positively associated with in vitro invasiveness and inversely associated with metastatic potential, adherence, and in vivo growth rate. These results suggest that at least within one tumor model, a negative association occurs between metastatic potential and β1-6 branched oligosaccharide expression. In these studies two metastatic variants, Cl-66M1 and Cl-66M2, were selected following serial in vivo passage of Cl-66, a clonal cell line obtained from a mouse mammary adenocarcinoma cell line. The parent cell line and the two metastatic variants were approximately equal in their adherence to fibronectin, laminin, and collagen type IV coated plastic. In contrast, both Cl-66M1 and Cl-66M2 had a significantly increased ability to invade through matrigel invasion chambers and expressed significantly increased levels of β1-6 branched, N-linked carbohydrates, and sialic acid compared to the clonal parental cell line, Cl-66. Furthermore, the in vivo tumor growth rates of these selected variants were decreased compared to Cl-66 with the longest tumor volume doubling time observed with Cl-66M2.