Biomarkers CD44 and CD24 are routinely used to identify breast cancer stem cells (BCSCs). BCSCs are chemotherapy resistant and bear high tumorigenesis and metastatic capabilities. Wnt/β-catenin signaling is involved in maintaining CSCs and thus is responsible for recurrence and poor prognosis. Role of Wnt receptor LRP6 in breast cancer promotion and progression is well known. We hypothesized that interactions between cancer cells, macrophages, and endothelial cells induce cancer stemness via activation of Wnt/-β catenin pathway, and blocking that pathway will reduce primary and metastatic tumors.
Breast cancer cells were co-cultured with macrophages and endothelial cells with or without Wnt inhibitors. BCSC markers were quantified by flowocytometry. CD44+/CD24- cells were FACS sorted and applied to 3D cultures with or without Wnt inhibitors and/or Doxorubicin. In our
Co-culture of breast cancer cells with macrophages and/or endothelial cells, significantly increases cells expressing BCSC markers, while inhibition of Wnt receptor significantly reduced them. The CD4+/24- cells are found highly resistant to Doxorubicin both in 2D and 3D cultures. In our
Inhibition of Wnt pathway significantly reduces the induction of BCSCs
Sumanta Goswami1,2, Gargi Bandopadhyaya1, Justin Stein1, Srinjoy Goswami1, John S. Condeelis2 and Maja H. Oktay2,3
1Department of Biology, Yeshiva University, New York, NY 10033. 2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461 3Department of Pathology Montefiore Medical Center, Bronx, NY 10467
Sumanta Goswami
Has not received any funding
All authors have declared no conflicts of interest.