IGFBP2 secretion by mammary adipocytes limits breast cancer invasion
Menée à l'aide de lignées cellulaires, d'une xénogreffe sur un modèle murin et d'échantillons de tissus mammaires sains ou cancéreux d'origine humaine, cette étude met en évidence un mécanisme par lequel la sécrétion de la protéine de liaison IGFBP2 par les adipocytes mammaires limite la progression tumorale
The progression of noninvasive ductal carcinoma in situ to invasive ductal carcinoma for patients with breast cancer results in a significantly poorer prognosis and is the precursor to metastatic disease. In this work, we have identified insulin-like growth factor–binding protein 2 (IGFBP2) as a potent adipocrine factor secreted by healthy breast adipocytes that acts as a barrier against invasive progression. In line with this role, adipocytes differentiated from patient-derived stromal cells were found to secrete IGFBP2, which significantly inhibited breast cancer invasion. This occurred through binding and sequestration of cancer-derived IGF-II. Moreover, depletion of IGF-II in invading cancer cells using small interfering RNAs or an IGF-II–neutralizing antibody ablated breast cancer invasion, highlighting the importance of IGF-II autocrine signaling for breast cancer invasive progression. Given the abundance of adipocytes in the healthy breast, this work exposes the important role they play in suppressing cancer progression and may help expound upon the link between increased mammary density and poorer prognosis. Adipocyte-derived IGFBP2 from healthy stroma effectively limits IGF-II-driven breast cancer progression.
Science Advances 2023