Procathepsin D interacts with prosaposin in cancer cells but its internalization is not mediated by LDL receptor-related protein.
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| Abstract |
The cell surface binding, endocytosis, and lysosomal routing of procathepsin D (procath-D) in cancer cells are mostly independent of the mannose-6-phosphate (M6P) receptors. In an attempt to define the receptor involved, we intracellularly cross-linked procath-D with a 68-kDa protein that we identified with specific antibodies as prosaposin in human breast and ovarian cancer cell lines. In cancer cells, this protein-protein interaction was resistant to ammonium chloride or M6P treatment, indicating that it was independent of the M6P receptors. A similar interaction also occurred in the breast cancer cell culture medium between the secreted prosaposin and procath-D. Since these two precursors can be endocytosed, we then determined whether they were interacting with the same cell surface receptor. In fibroblasts, we confirmed that the endocytosis of these two proteins was different since it was generally mediated by the M6P receptors for procath-D and mostly by LRP (LDL receptor-related protein) for prosaposin. In breast cancer cells, prosaposin endocytosis was not detected, in contrast to procath-D endocytosis, suggesting that the majority of procath-D is not internalized as a complex with prosaposin. Moreover, RAP (receptor-associated protein), a ligand inhibiting LRP-mediated endocytosis, prevented internalization of prosaposin in 49-F rat fibroblasts, but did not affect procath-D M6P-independent internalization in MDA-MB231 cells. We conclude that in breast cancer cells, even though procath-D interacts intracellularly and extracellarly with prosaposin, it is endocytosed independent of prosaposin by a receptor different from the M6P receptors and the LRP.
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| Authors | Valérie Laurent-Matha, Annick Lucas, Silke Huttler, Konrad Sandhoff, Marcel Garcia, Henri Rochefort |
| Journal | Experimental cell research (Exp Cell Res) Vol. 277 Issue 2 Pg. 210-9 (Jul 15 2002) ISSN: 0014-4827 [Print] United States |
| PMID | 12083803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | (c) 2002 Elsevier Science (USA). |
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