Journal Article

Inhibition of Invasion and Metastasis by Glypican-3 in a Syngeneic Breast Cancer Model

Peters, M.G., Farías, E., Bal de Kier Joffé, E., Filmus, J., Puricelli, L., Colombo, L.

2003

Overview

Glypican-3 (GPC3), a proteoglycan bound to the cell membrane through a GPI anchor, is widely expressed in the embryo but down regulated in most adult tissues, with some exceptions as mammary cells. GPC3 is involved in the regulation of cell proliferation and survival in specific cell types. LM3, a murine mammary tumor cell line unable to express GPC3, was stably transfected with the rat GPC3 gene to analyze its role in tumor progression. Upon injection into syngeneic BALB/c mice LM3-GPC3 clones showed less local invasiveness and developed fewer spontaneous and experimental lung metastasis than controls. GPC3-expressing cells were more sensitive to apoptosis induced by serum depletion, exhibited a delay in the first steps of spreading and were less motile than controls. On the other hand, LM3-GPC3 cells were significantly more adherent to FN than control ones. We observed that GPC3 transfectants presented a higher expression of E-cadherin and beta-catenin, molecules whose down regulation has been associated with tumor progression. Exogenous TGF-beta increased MMP-9 activity in both control and GPC3-expressing cells, but did not modulate MMP-2. Contrarily, GPC3 expression prevented the increase of MMP-2 activity induced by IGF-II. Our results suggest that GPC3 has a protective role against mammary cancer progression.

• Publisher: Springer,Springer Nature B.V
• Subject: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Animals / Applied cell therapy and gene therapy / beta Catenin / Biological and medical sciences / Blotting, Northern / Blotting, Western / Breast cancer / Cadherins - metabolism / Cancer research / Cancer therapies / Cell Line, Tumor / Cytoskeletal Proteins - metabolism / Disease Models, Animal / Female / Glypicans / Heparan Sulfate Proteoglycans - genetics / Heparan Sulfate Proteoglycans - metabolism / Immunohistochemistry / Insulin-Like Growth Factor II - pharmacology / Lung Neoplasms - metabolism / Lung Neoplasms - secondary / Mammary Neoplasms, Animal - metabolism / Mammary Neoplasms, Animal - pathology / Medical sciences / Mice / Mice, Inbred BALB C / Neoplasm Invasiveness / Neoplasm Metastasis / Rats / Trans-Activators - metabolism / Transfection / Transforming Growth Factor beta - pharmacology / Transfusions. Complications. Transfusion reactions. Cell and gene therapy