Tissue inhibitor of metalloproteinase-3 expression is upregulated during human cytotrophoblast invasion in vitro
Kathryn E. Bass
Department of Stomatology, University of California at San Francisco, San Francisco
Search for more papers by this authorHongxia Li
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco
Search for more papers by this authorSusan P. Hawkes
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco
Search for more papers by this authorEric Howard
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City
Search for more papers by this authorElizabeth Bullen
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City
Search for more papers by this authorThien-Khai H. Vu
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City
Search for more papers by this authorMichael McMaster
Department of Stomatology, University of California at San Francisco, San Francisco
Search for more papers by this authorMary Janatpour
Department of Stomatology, University of California at San Francisco, San Francisco
Search for more papers by this authorCorresponding Author
Susan J. Fisher
Department of Stomatology, University of California at San Francisco, San Francisco
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco
Department of Anatomy, University of California at San Francisco, San Francisco
HSW 604, University of California, San Francisco, San Francisco, CA 94143-0512Search for more papers by this authorKathryn E. Bass
Department of Stomatology, University of California at San Francisco, San Francisco
Search for more papers by this authorHongxia Li
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco
Search for more papers by this authorSusan P. Hawkes
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco
Search for more papers by this authorEric Howard
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City
Search for more papers by this authorElizabeth Bullen
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City
Search for more papers by this authorThien-Khai H. Vu
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City
Search for more papers by this authorMichael McMaster
Department of Stomatology, University of California at San Francisco, San Francisco
Search for more papers by this authorMary Janatpour
Department of Stomatology, University of California at San Francisco, San Francisco
Search for more papers by this authorCorresponding Author
Susan J. Fisher
Department of Stomatology, University of California at San Francisco, San Francisco
Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco
Department of Anatomy, University of California at San Francisco, San Francisco
HSW 604, University of California, San Francisco, San Francisco, CA 94143-0512Search for more papers by this authorAbstract
Surprisingly, a successful human pregnancy requires cells from the fetal portion of the placenta (cytotrophoblasts) to adopt tumor-like properties. Cytotrophoblasts attach the conceptus to the endometrium by invading the uterus, and they initiate blood flow to the placenta by breaching maternal vessels. But unlike tumor metastasis, cytotrophoblast invasion is highly regulated both spatially and temporally. Our previous work showed that matrix metalloproteinase-9 (MMP-9) expression is upregulated during cytotrophoblast differentiation along the invasive pathway, and that activity of this proteinase specifies the cells' ability to degrade extracellular matrix (ECM) substrates in vitro. Here we tested the hypothesis that invading cytotrophoblasts express an unusual tissue inhibitor of metalloproteinase (TIMP) repertoire that allows them to regulate their MMP-9 proteolytic activity. By using protease-substrate gel electrophoresis, we found that human cytotrophoblasts express primarily TIMP-3. We showed that the cells' TIMP-3 expression is regulated in accord with that of MMP-9. The highest levels of protein and mRNA for both these molecules were detected after differentiation to a fully invasive phenotype and during early gestation, when invasion peaks, rather than at term, when invasion has stopped. Our results suggest that coexpression of MMP-9 and TIMP-3 by invading cytotrophoblasts plays an important role in regulating the depth of uterine invasion. Dev. Genet. 21:61–67, 1997. © 1997 Wiley-Liss, Inc.
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