Adipocytes help to hold back breast cancer

Researchers from the University of Turku’s InFLAMES Flagship, Turku Bioscience Centre and Turku University Hospital have revealed that healthy fat cells in the breast, also known as adipocytes, secrete a potent factor known as insulin-like growth factor-binding protein 2 (IGFBP2), which acts as a barrier against invasive breast cancer progression. Their findings seemingly turn conventional wisdom on its head, as adipocytes are generally thought to promote cancer progression. The discovery has been published in the journal Science Advances.

Breast cancer patients who experience the transition from pre-malignant ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) face a considerably poorer prognosis and an increased risk of developing metastatic disease. The research team focused on identifying factors that impede this invasive progression, with IGFBP2 emerging as a key factor secreted by healthy adipocytes.

“This study demonstrates that healthy breast fat can play a protective role in the maintenance of tissue homeostasis and cancer containment,” said Dr Emilia Peuhu, a key collaborator on the study.

In addition to the loss of adipocytes that occurs as women age, the study found that older women had reduced expression of IGFBP2, suggesting that the anticancer activities of breast adipocytes might also decrease with age. InFLAMES group leader Professor Johanna Ivaska, the principal investigator on the project, said the team were astonished at the findings.

“Increasing age and higher breast density, with fewer adipocytes, are two well-established risk factors for the development of breast cancer,” Ivaska said. “Our research provides a possible explanation for this increased risk, as we found that IGFBP2 levels are also reduced in older individuals and that healthy breast adipocytes can secrete factors, such as IGFBP2, to inhibit tumour progression.”

The implications of this discovery extend to the understanding of mammary density and its connection with poorer prognosis. Postdoctoral researcher James Conway, the lead researcher on the project, noted, “While restoring IGFBP2 into the mammary environment might not be possible, the use of antibody-based inhibitors of IGF-II could help to contain non-invasive breast lesions by acting in a similar fashion to IGFBP2 itself, which we have already observed in our model systems.”

The team is now exploring the therapeutic avenues that have opened up as a result of these findings.

Image credit: iStock.com/bymuratdeniz