Multiple lysosomal trafficking phenotypes in metastatic mouse mammary tumor cell lines.
Although altered synthesis and trafficking of lysosomal proteins and their receptors are associated with a wide range of human and rodent malignancies, the basis for their involvement remains obscure. Here we describe findings on a set of mouse mammary tumor cell lines that we are using as a model to study the role of these proteins in oncogenesis and tumor progression. Three distinct proteinase-secreting phenotypes were identified among the metastatic cell lines of the set. Two phenotypes displayed a high level of secretion of cathepsin L and the third was characterized by elevated secretion of matrix metalloproteinase 9 (MMP-9). The two cathepsin L-secreting phenotypes were distinct in that they displayed differences in cathepsin trafficking, expression of mannose 6-phosphate/insulin-like growth factor receptor and expression of proliferin, a mannose-phosphorylated angiogenic factor. Although cells representing all three phenotypes are capable of dissemination to distant organs when implanted into mouse mammary glands, only cells with the MMP-9 phenotype were found to be capable of direct intravasation. These findings indicate that multiple proteinase-secreting phenotypes can arise from the same tumor and suggest that cathepsin L and other lysosomal proteins may play a role in dissemination of tumor cells via the lymphatic system.
Tao
K
K
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Li
J
J
Warner
J
J
MacLeod
K
K
Miller
F R
FR
Sahagian
G G
GG
D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D008247:Lysosomes / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D010641:Phenotype; D010960:Plasminogen Activators / Q000378:metabolism; D016133:Polymerase Chain Reaction; D021381:Protein Transport / Q000502:physiology*; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D017527:Receptor, IGF Type 2; D002403:Cathepsins; D010960:Plasminogen Activators; D008666:Metalloendopeptidases