Production of insulin‐like growth factor‐II (MSA) by endoderm‐like cells derived from embryonal carcinoma cells: Possible mediator of embryonic cell growth

Abstract

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 [125I]iodo multiplication stimulating activity (MSA) binding to PYS cells. MSA is the rat homologue of human IGF-II. The high molecular weight fraction (Mr approximately 60K) apparently corresponds to IGF-binding protein as determined by its ability to bind [125I]iodo-MSA. The low molecular weight fraction (Mr approximately 8K) is biologically active as this fraction stimulates [3H]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.

Differentially regulated production of platelet-derived growth factor and of transforming growth factor beta by a human teratocarcinoma cell line

“…There are several reports on the role of growth factors in these processes (for a recent review see [23]). Production of insulin-like growth factors (IGFs) is a general observation for differen-* To whom offprint requests should be sent tiated EC cells, but reduced levels of production have also been observed in the undifferentiated stem cells [32,411. Gudas et al [I71 and Rizzino and Bowen-Pope [37] reported the production of a platelet-derived growth factor-like (PDGF-like) protein by PSA-IG, F9, and PC13 EC cells.…”

Gene therapy of murine teratocarcinoma: separate functions for insulin-like growth factors I and II in immunogenicity and differentiation.

“…Human and mouse teratocarcinoma cell lines produce IGF-I and the type I IGF receptor (15,(18)(19)(20). Teratocarcinoma consists of malignant undifferentiated embryonic carcinoma (EC) cells and various somatic tissue intermingled (21,22).…”

Differentiation‐dependent production of a platelet‐derived growth factor‐like mitoattractant by endoderm cells derived from embryonal carcinoma cells

“…Isacke and Deller (1983) and Rizzino et al (1983) have reported that coculture of undifferentiated embryonal carcinoma cells with established fibroblast cells supported the growth of the fibroblasts, apparently owing to growth factors secreted into the culture medium by the stem cells. Recently, Heath and Isacke (1984) reported the isolation of a growth factor from medium conditioned by PC 13 embryonal carcinoma stem cells, and we have shown that Dif 5 endoderm and visceral endoderm-like PSA6E cells secrete significant amounts of IGF-I1 (Nagarajan et al, 1985). Gudas et al (1983) and Rizzino and Bowen-Pope (1985) have reported that undifferentiated teratocarcinoma stem cells secrete a PDGF-related growth factor.…”