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Production of insulin‐like growth factor‐II (MSA) by endoderm‐like cells derived from embryonal carcinoma cells: Possible mediator of embryonic cell growth
Author(s) -
Nagarajan Lalitha,
Anderson Wayne B.,
Nissley S. Peter,
Rechler Matthew M.,
Jetten Anton M.
Publication year - 1985
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041240205
Subject(s) - embryonic stem cell , mediator , endoderm , growth factor , microbiology and biotechnology , cell growth , biology , insulin like growth factor , endocrinology , medicine , cancer research , biochemistry , receptor , gene
The present study was carried out to determine if an insulin‐like growth factor (IGF) type activity might be produced by embryonal carcinoma‐derived cells. The cell line used to condition growth medium for the isolation of secreted growth factors was a newly established Dif 5 cell type. Dif 5 cells are a differentiated endoderm‐like cell type derived from F9 embryonal carcinoma cells (which possess properties similar to mouse embryonic stem cells) following extensive exposure to retinoic acid. When growth medium conditioned by Dif 5 cells is chromatographed on Sephadex G‐75 in 1 M acetic acid two peaks of activity are observed which compete for specific [ 125 I]iodo multiplication stimulating activity (MSA) binding to PYS cells. MSA is the rat homologue of human IGF‐II. The high molecular weight fraction (Mr ˜ 60K) apparently corresponds to IGF‐binding protein as determined by its ability to bind [ 125 I]iodo‐MSA. The low molecular weight fraction (Mr ˜ 8K) is biologically active as this fraction stimulates [ 3 H]thymidine incorporation into serum‐starved chick embryo fibroblasts. Radioimmunoassay data indicate that the IGF‐like activity produced by Dif 5 cells is more closely related to IGF‐II than to IGF‐I. Undifferentiated embryonal carcinoma stem cell lines (F9, Nulli, and PCC4) produced little of this MSA‐like activity, while PYS‐2 (parietal endoderm‐like) cells produced about 16 ng MSA/10 6 cells/24 hr as determined by radioimmunoassay. Dif 5 and PSA‐5E (visceral endoderm‐like) cells, are found to secrete significant amounts of MSA into the growth medium (30–50 ng MSA/10 6 cells/24 hr). These findings offer further support to a proposal that MSA (IGF‐II) produced by endoderm cells, particularly visceral endoderm, may serve as an early embryonic growth factor.