Counterintuitive production of tumor-suppressive secretomes from Oct4- and c-Myc-overexpressing tumor cells and MSCs
Kexin Li, Xun Sun, Rongrong Zha, Shengzhi Liu, Feng Yan, Tomonori Sano, Uma K. Aryal, Akihiro Sudo, Bai‐Yan Li, Hiroki Yokota
Abstract
Background: Advanced breast cancer frequently metastasizes to bone, but inhibiting tumor progression in chemotherapy may occasionally enhance tumorigenesis. Here, we employed a counterintuitive approach of overexpressing Yamanaka factors (Oct4, c-Myc, Sox2, and Klf4) and examined a conditioned medium (CM)-based treatment option with induced tumor-suppressing cells (iTSCs). Methods: In vitro proliferation and migration assays were conducted using tumor cell lines derived from breast cancer, as well as prostate and pancreatic cancers, and osteosarcoma. The tumor-suppressing capability of iTSC-derived CM was evaluated using freshly isolated breast cancer tissues and a mouse model of mammary tumors and tumor-induced osteolysis. The regulatory mechanism was evaluated using Western blotting, immunoprecipitation, pull-down, gene overexpression, and RNA interference based on mass spectrometrybased proteomics data.