Tumor-promoting phorbol esters support the in vitro proliferation of murine pluripotent hematopoietic stem cells

J. L. Spivak, B. B. Hogans, R. K. Stuart

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of tumor-promoting phorbol esters on the in vitro proliferation of mouse pluripotent hematopoietic stem cells (CFU-S) was examined using a short-term in vitro culture system and an 11-d spleen colony assay. Phorbol myristate acetate (PMA, 10-7 M), but not the inert compound phorbol, supported the in vitro survival of day 11 CFU-S for 72 h in a manner similar to IL 2. PMA also enhanced the effect of IL 3 on the in vitro survival of day 11 CFU-S and as little as 1 h of exposure to PMA was sufficient for this purpose. The effect of PMA on CFU-S survival in vitro was not mediated by prostaglandins, did not require an established adherent cell population, and was observed at a concentration of 10-9 M. PMA alone did not enhance the in vitro survival of day 11 CFU-S at very low concentrations of FCS but was still able to potentiate the effect of IL 3 on these cells. PMA also enhanced the in vitro survival of day 11 CFU-S from mice treated with 5-fluorouracil or from marrow cells exposed to merocyanine 540 and light. The interaction of PMA with day 11 CFU-S was not inhibited by a neutralizing antiserum to IL 3 but was inhibited by the protein kinase inhibitor H-7. Together, the data indicate that tumor-promoting phorbol esters interact with pluripotent hematopoietic stem cells. Like IL 3, their effect appears to be permissive and involves stem cells with marrow repopulating ability.

Original languageEnglish (US)
Pages (from-to)100-107
Number of pages8
JournalJournal of Clinical Investigation
Volume83
Issue number1
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Medicine(all)

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