Abstract

Stromal-epithelial interactions modulate growth and development in normal and neoplastic mammary gland. The release of IGF binding proteins (IGFBPs) by the stromal compartment of the mammary gland may play a modulating role in the IGF-mediated proliferation of mammary epithelium. Therefore, the IGFBP-expression pattern of the canine mammary tumor cell line U335 (CMT-U335), which has a mesenchymal phenotype, was determined. In addition, the effects of IGFs and all trans retinoic acid (RA) on DNA synthesis, and IGFBP secretion and distribution were examined. The IGFBPs secreted by CMT-U335 were characterized as IGFBP-2, -4, -5, and -6. Moreover, CMT-U335 appeared to be a suitable mammary mesenchymal cell line for study of the regulatory factors of IGFBP expression and the mechanism(s) involved. IGFs and RA enhanced IGFBP concentrations in cell-conditioned medium with IGF-I and RA having an additive effect. The IGF-I-stimulated DNA synthesis, however, was inhibited by RA. The difference between IGF-I and RA was an enhanced IGFBP-5 binding to the extracellular matrix (ECM) by RA, whereas IGF-I reduced binding to the ECM. Because high doses of insulin had no significant effects on IGFBP concentrations in the medium, it is concluded that IGF-I-induced changes in IGFBP concentrations are not mediated by type-I IGF receptors and may be the consequence of IGFBP redistribution.

Keywords

dog; IGF; IGFBP; mammary mesenchymal cell line; retinoic acid

Published in

Breast Cancer Research and Treatment
1999, Volume: 54, number: 1, pages: 11-23
Publisher: KLUWER ACADEMIC PUBL

SLU Authors

• Hellmén, Eva

  • Department of Pathology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Pathobiology


Publication identifier

DOI: https://doi.org/10.1023/A:1006107703745

Permanent link to this page (URI)

https://res.slu.se/id/publ/64781