Effects of two monoclonal antibodies, MLS128 against Tn-antigen and 1H7 against insulin-like growth factor-I receptor, on the growth of colon cancer cells

Abstract

MLS128 is an anti-carbohydrate monoclonal antibody (mAb) that binds three or two consecutive Tn-antigens. MLS128 bound 110-210 kDa glycoproteins (GPs) and inhibited the growth of LS180 and HT29 colon and MCF-7 breast cancer cells. One possible mechanism of MLS128's inhibition of growth may be via insulin-like growth factor-I receptor (IGF-IR) down-regulation (Morita et al. BioSci Trends. 2009; 3:32-37). The current study examined the role of IGF-IR signaling in the growth of colon cancer cells and its possible interaction with MLS128-induced inhibition of cell growth in LS180, LS174T, and HT29 human colon cancer cells treated with MLS128 or anti-IGF-IR 1H7. Both MLS128 and 1H7 treatment significantly inhibited the growth of colon cancer cells. All three colon cancer cell lines expressed IGF-IR. Their growth was in part IGF-I dependent, but inhibition by MLS128 was independent of IGF-IR signaling. All of the colon cancer cell lines expressed an 110 kDa GP for MLS128 binding, but MCF-7 cells expressed MLS128-detectable bands with higher molecular masses. 1H7 treatments caused down-regulation of IGF-IR but did not affect 110 kDa GP levels. MLS128 treatments resulted in partial disappearance of the 110 kDa band but did not affect IGF-IR levels. Western blotting analyses of colon and breast cancer cell lysates revealed that colon and breast cancer cells differed significantly in patterns of expression of growth-related molecules while colon cancer cells were similar but distinctive. In conclusion, MLS128 inhibited the growth of colon cancer cells by binding to the 110 kDa GP receptor. Inhibition of growth by MLS128 did not appear to affect IGF-IR signaling and instead only affected other growth signaling pathways.