{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:52:45Z","timestamp":1767855165685,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":6731,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1986,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the presence of methotrexate, cultured human choriocarcinoma (BeWo) cells undergo a differentiative response that resembles normal trophoblastic development. In the current study, the effects of cell number and population density on drug\u2010induced conversion of BeWo cells from the cytotrophoblast\u2010like to the syncytiotrophoblastlike phenotype were investigated using as markers of differentiation formation of \u201cgiant\u201d cells, a process shown to require exogenous purines, and expression of placental (heat\u2010stable) alkaline phosphatase. Giant cell formation, assessed by determination of cell volumes, was reduced in crowded cultures, and addition of hypoxanthine to growth media partially restored methotrexate\u2010induced cell enlargement. Cellular uptake of methotrexate, assessed by following the loss of methotrexate from cell culture fluids during drug exposures, was two\u2010threefold greater in sparsely populated than in densely populated cultures. Although the concentration of methotrexate in culture fluids of crowded cultures declined during exposures of 48 hr, the amount of extracellular drug remaining at 48 hr was well above the threshold for induction of the differentiative response. When culture population was held constant and population density was manipulated by varying the substratum available to cells, methotrexate\u2010induced cell enlargement was inversely related to population density. Expression of placental alkaline phosphatase, salvage of exogenous hypoxanthine, and synthesis of RNA were also reduced at high population densities. These results indicate that expression of markers of methotrexate\u2010induced differentiation of BeWo cells was inhibited in a density\u2010dependent manner that may have been related to reduced cellular uptake of the inducing agent and of exogenous nutrients (purines) from culture fluids.<\/jats:p>","DOI":"10.1002\/jcp.1041280305","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T12:33:31Z","timestamp":1109421211000},"page":"375-382","source":"Crossref","is-referenced-by-count":15,"title":["Density\u2010dependent inhibition of expression of syncytiotrophoblastic markers by cultured human choriocarcinoma (BeWo) cells"],"prefix":"10.1002","volume":"128","author":[{"given":"Neal S.","family":"Burres","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol E.","family":"Cass","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(54)90176-7"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600710119"},{"key":"e_1_2_1_5_1","first-page":"16","article-title":"The cytodifferentiative response of a cultured human choriocarcinoma cell line (BeWo) is dependent on inhibition of folate\u2010dependent biosynthetic pathways","volume":"24","author":"Burres N. 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