Li, KexinHuo, QingjiLi, Bai-YanYokota, Hiroki2023-10-242023-10-242023-01-18Li K, Huo Q, Li BY, Yokota H. The Double-Edged Proteins in Cancer Proteomes and the Generation of Induced Tumor-Suppressing Cells (iTSCs). Proteomes. 2023;11(1):5. Published 2023 Jan 18. doi:10.3390/proteomes11010005https://hdl.handle.net/1805/36591Unlike a prevalent expectation that tumor cells secrete tumor-promoting proteins and stimulate the progression of neighboring tumor cells, accumulating evidence indicates that the role of tumor-secreted proteins is double-edged and context-dependent. Some of the oncogenic proteins in the cytoplasm and cell membranes, which are considered to promote the proliferation and migration of tumor cells, may inversely act as tumor-suppressing proteins in the extracellular domain. Furthermore, the action of tumor-secreted proteins by aggressive "super-fit" tumor cells can be different from those derived from "less-fit" tumor cells. Tumor cells that are exposed to chemotherapeutic agents could alter their secretory proteomes. Super-fit tumor cells tend to secrete tumor-suppressing proteins, while less-fit or chemotherapeutic agent-treated tumor cells may secrete tumor-promotive proteomes. Interestingly, proteomes derived from nontumor cells such as mesenchymal stem cells and peripheral blood mononuclear cells mostly share common features with tumor cell-derived proteomes in response to certain signals. This review introduces the double-sided functions of tumor-secreted proteins and describes the proposed underlying mechanism, which would possibly be based on cell competition.en-USAttribution 4.0 InternationalConditioned mediumInduced tumor-suppressing cellsiTSCsProteomesArticle