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Growth advantage of human leiomyoma cells compared to normal smooth‐muscle cells due to enhanced sensitivity toward insulin‐like growth factor I
Author(s) -
Van Der Ven Leo T. M.,
Gloudemans Ton,
Roholl Paul J. M.,
Van BuulOffers Sylvia C.,
Bladergroen Bellinda A.,
Welters Marij J. P.,
Sussenbach John S.,
Otter Willem Den
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910590323
Subject(s) - myometrium , endocrinology , leiomyoma , receptor , medicine , immunostaining , smooth muscle tissue , uterine leiomyoma , growth factor , biology , internalization , epidermal growth factor , immunohistochemistry , insulin like growth factor , smooth muscle , uterus , pathology
Human uterine leiomyomas exhibit increased IGF‐I binding compared to myometrium, while both tissues show IGF‐I gene expression. In this study we have examined the functional importance of these findings by testing the presence of IGF‐I in 15 leiomyoma biopsies and in 18 myometrium biopsies and the capacity of smooth‐muscle cells cultured from these tissues to react to IGF‐I. The mean IGF‐I peptide concentration in leiomyomas was 3 times higher than in myometrium. This resulted from increased IGF‐I uptake in leiomyomas rather than from increased synthesis, as these tissues contain higher concentrations of type‐IIGF receptors, as detected by immunohistochemistry, and equal levels of IGF‐I mRNA. Blocking IGF‐I transport with cytochalasin‐B and with the type‐I IGF receptor blocking antibody αIR3 in cultured cells induced decreased immunostaining intensity for IGF‐I in most myometrium and leiomyoma cultures, indicating that the detected IGF‐I is internalized. Depending on the culture conditions, IGF‐I administration yielded increased survival or a higher proliferation rate in leiomyoma cultures than in myometrium cultures, indicating the increased importance of exogenous IGF‐I for the growth of transformed smooth‐muscle cells. We conclude that the increased concentrations of type‐I IGF receptors in leiomyoma compared to myometrial smooth‐muscle cells are functional with respect to the enhanced internalization of IGF‐I and that they provide these tumor cells with a growth advantage compared to their normal counterparts. © 1994 Wiley‐Liss, Inc.