Maspin is an intracellular serpin that partitions into secretory vesicles and is present at the cell surface.
The tumor suppressor maspin (mammary serpin) was originally identified as a component of human mammary epithelial cells that is downregulated as mammary tumor cells progress from the benign to the invasive and metastatic states. Maspin inhibits cellular invasion, motility, and proliferation, but its mechanism of action is currently unknown. Because the cellular machinery responsible for these processes is cytoplasmic, we have reexamined the tissue distribution and subcellular localization of maspin. We find that maspin, or a maspin-like protein, is present in many human organs, in which it localizes to epithelia. In cultured human mammary myoepithelial cells, maspin is predominantly a soluble cytoplasmic protein that associates with secretory vesicles and is present at the cell surface. In vitro assays show that the vesicle association is due to the existence of an uncleaved facultative secretion signal that allows small amounts of maspin to partition into the endoplasmic reticulum. These results demonstrate that maspin is more widespread than previously believed. The subcellular localization studies indicate that soluble intracellular and vesicle-associated maspin probably play an important role in controlling the invasion, motility, and proliferation of cells expressing it, whereas extracellular maspin may also regulate these processes in adjacent cells.
Pemberton
P A
PA
LXR Biotechnology, Inc., Richmond, California 94804, USA.
Tipton
A R
AR
Pavloff
N
N
Smith
J
J
Erickson
J R
JR
Mouchabeck
Z M
ZM
Kiefer
M C
MC
D015152:Blotting, Northern; D001940:Breast / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004848:Epithelium / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins