IGFBP2 secretion by mammary adipocytes limits breast cancer invasion

James R.W. Conway*, Defne D. Dinç, Gautier Follain, Oona Paavolainen, Jasmin Kaivola, Pia Boström, Pauliina Hartiala, Emilia Peuhu, Johanna Ivaska*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)
5 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article numbereadg1840
Number of pages15
JournalScience Advances
Volume9
Issue number28
DOIs
Publication statusPublished - 12 Jul 2023
MoE publication typeA1 Journal article-refereed

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