Abstract
To assess the role of insulin-like growth factors (IGFs) in growth and transformation of normal (myometrium) and tumorous smooth muscle cell (SMC) tissues, in situ hybridization (ISH) analysis for insulin-like growth factor I and II (IGF-I and IGF-II) mRNAs was combined with detection of IGF peptides, their receptors and IGF binding protein-3 (IGFBP-3). mRNAs for both IGFs were detected in smooth muscle cells in normal, benign and malignant SMC tissues, together with the IGF peptides, both IGF receptors and IGFBP-3. This suggests an autocrine role for both IGFs. Leiomyomas had higher IGF-I peptide levels and higher levels of type I IGF receptors than myometrium, supporting the idea that IGFs play a role in the growth and transformation of these tumours. Low-grade leiomyosarcomas contained more IGF-II mRNAs than myometrium and leiomyoma, fewer type II IGF/mannose 6-phosphate receptors and less IGFBP-3 than myometrium and, in addition, fewer IGF-I mRNAs and type I IGF receptors than leiomyoma. Intermediate- and high-grade leiomyosarcomas had intermediate levels of IGF-II mRNAs and peptide, ranging between those in myometrium and low-grade leiomyosarcomas. Thus, growth and transformation of leiomyosarcomas may be regulated by IGF-II, although more markedly in low-grade than in high-grade leiomyosarcomas. In conclusion, the various categories of SMC tissues are associated with a distinct expression pattern of the IGF system. This suggests that each category of SMC tumours arises as a distinct entity and that there is no progression of transformation in these tissues.
Highlights
We have previously shown that higher insulin-like growth factors (IGFs)-I concentrations in leiomyoma than in myometrium may be as a result of the higher levels of type I IGF receptors in leiomyoma (Van der Ven et al, 1994)
In situ hybridization showed that in myometrium both IGF-I and IGF-II mRNAs are distributed in a whirling pattern, whereas the distribution in leiomyoma shows a more uniform pattern
The first question of this study addresses the site of production of IGFs in smooth muscle tissues
Summary
Tissue collectionNormal and benign smooth muscle tissues were obtained from the uteri of patients that had undergone hysterectomy to treat leiomyoma. Part of the tissue was snap-frozen in liquid nitrogen and stored at -80°C for further use in mRNA or peptide extraction procedures and for immunohistochemistry. Another part was routinely fixed in 4% phosphate-buffered formaldehyde (Klinipath, Duiven, The Netherlands), dehydrated through a graded ethanol/xylene series and embedded in paraffin. Loss of expression of smooth muscle markers in leiomyosarcomas is a common event in these tumours (Roholl et al, 1990). Tumours with a high percentage of necrosis (>50%) were excluded from assays in which vitality of the tissue could not be checked.
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