Department of Applied Biochemistry, Tokai University School of Engineering, Hiratsuka, Kanagawa, Japan.
Biosci Trends. 2012 Dec;6(6):303-12.
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. BioScience 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 110kDa 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 110kDa GP levels. MLS128 treatments resulted in partial disappearance of the 110kDa 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 110kDa GP receptor. Inhibition of growth by MLS128 did not appear to affect IGF-IR signaling and instead only affected other growth signaling pathways.
MLS128 是一种抗碳水化合物单克隆抗体 (mAb)，可与三个或两个连续的 Tn 抗原结合。MLS128 结合 110-210 kDa 糖蛋白 (GP)，并抑制 LS180 和 HT29 结肠和 MCF-7 乳腺癌细胞的生长。MLS128 抑制生长的一种可能机制可能是通过胰岛素样生长因子-I 受体 (IGF-IR) 下调（Morita 等人，BioScience Trends. 2009; 3:32-37）。本研究探讨了 IGF-IR 信号在结肠癌细胞生长中的作用及其与 MLS128 诱导的 LS180、LS174T 和 HT29 人结肠癌细胞生长抑制的相互作用，这些细胞用 MLS128 或抗 IGF-IR 1H7 处理。MLS128 和 1H7 处理均显著抑制结肠癌细胞的生长。三种结肠癌细胞系均表达 IGF-IR。它们的生长部分依赖于 IGF-I，但 MLS128 的抑制与 IGF-IR 信号无关。所有结肠癌细胞系均表达 MLS128 结合的 110kDa GP，但 MCF-7 细胞表达 MLS128 可检测到更高分子量的带。1H7 处理导致 IGF-IR 下调，但不影响 110kDa GP 水平。MLS128 处理导致 110kDa 带部分消失，但不影响 IGF-IR 水平。对结肠和乳腺癌细胞裂解物的 Western 印迹分析表明，结肠和乳腺癌细胞在生长相关分子的表达模式上存在显著差异，而结肠癌细胞相似但具有特征性。总之，MLS128 通过与 110kDa GP 受体结合抑制结肠癌细胞的生长。MLS128 对生长的抑制似乎不影响 IGF-IR 信号，而仅影响其他生长信号通路。
