Alda Oddgeirsdóttir, Guðrún Valdimarsdóttir and Vera Varis
Introduction
Breast cancer is a common cause of cancer-related death in women. The interplay between breast cancer cells and the microenvironment is still poorly understood. Thrombospondin-1 (TSP-1) is an extracellular secreted glycoprotein and a natural inhibitor of blood vessel formation (angiogenesis). Our preliminary data suggests that TSP-1 is induced by TGFβ in resting endothelial cells and upon secretion, it represses breast cancer cell growth. TSP-1 has two receptors, CD36 and CD47, both of which have been implicated as important players in cancer progression.
Methods
We reason that the interaction between secreted proteins EGFL7 and TSP-1 and the receptors, CD36 and CD47, play pivotal role in tumor progression and that they are differentially expressed between tumor subtypes. To test this hypothesis, we will use tumor organoids (tumoroids) which are 3D cultures of patient-derived cancer cells and can serve as a miniature of the patient’s organs in vivo. Two breast cancer tumoroid subtypes, luminal A and triple-negative, and corresponding cancer cell lines will be used.
Results
The results indicate that TSP-1 reduces breast cancer cell proliferation rather than promoting apoptosis. The possible involvement of the CD36 and CD47 receptors in this reduction will be presented. The direct effect of endothelial cells on tumoroids in a co-culture will be introduced.
Conclusions
Subtypes of breast cancer can be assessed, with respect to the main factors of the TGFβ signal transduction in tumoroids which would enable us to understand why breast cancer subtypes respond differently to the same drug treatment.
