Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line.
During human placentation, extravillous cytotrophoblast cells emerge from chorionic villi contacting the decidua to invade the uterine wall. When isolated from first-trimester placentae, cytotrophoblast cells undergo step-wise differentiation in vitro that recapitulates the phenotypic heterogeneity observed in vivo. We examined a cell line, HTR-8/SVneo, that has been established from human first-trimester cytotrophoblast to determine whether these cells possess some of the unique cytotrophoblast characteristics that have been described previously. Exposure during serum-free culture to hypoxic conditions (2% oxygen concentration) increased HTR-8/SVneo cell proliferation and reduced invasion of a three-dimensional basement membrane (Matrigel). During culture on surfaces coated with individual extracellular matrix proteins, HTR-8/SVneo cells expressed cytokeratin but not the trophoblast-specific major histocompatibility protein, HLA-G. However, HLA-G expression was induced in HTR-8/SVneo cells that contacted Matrigel. Expression of the alpha5 integrin subunit was relatively unaffected by matrix composition, whereas alpha1 was up-regulated and alpha6 was down-regulated after transferring cells to Matrigel. Hypoxia increased alpha6 and decreased both alpha1 and HLA-G expression on Matrigel. HTR-8/SVneo cells retain several important characteristics associated with primary cultures of first-trimester human cytotrophoblast cells, including their altered behavior in response to a changing maternal environment.
Kilburn
B A
BA
Departments of Obstetrics and Gynecology and Anatomy and Cell Biology, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI 48201-1415, USA.
Wang
J
J
Duniec-Dmuchowski
Z M
ZM
Leach
R E
RE
Romero
R
R
Armant
D R
DR
Duniec-Dmuchkowski
Z M
ZM
D015703:Antigens, CD / Q000378:metabolism; D002455:Cell Division; D015687:Cell Hypoxia; D002460:Cell Line; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D039423:Integrin alpha1; D016023:Integrins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D039423:Integrin alpha1; D016023:Integrins; D019394:Ki-67 Antigen