Growth Factor double team promotes Breast Cancer

Cancer stem cells (CSCs) are thought to represent the origin of tumor development, but our knowledge about the basic mechanisms behind their self-renewal and differentiation remain relatively unknown. Breast cancer cells express and secrete nerve growth factor (NGF) and its precursor protein, with its own specific mode of action, proNGF, and so may be important components of the breast CSC niche. Now, in a study in Stem Cells, researchers from the laboratory of Xuefen Le Bourhis (Inserm, Université Lille, France) have found that NGF and proNGF promote symmetric divisions of quiescent CSCs and epithelial to mesenchymal transition (EMT), and thereby promoting breast cancer tumorigenesis. The common neurotrophins receptor p75NTR marks several adult stem cells [4], and regulates breast cancer cell survival and drug resistance, and so the authors studied this receptor as a possible mediator of NGF and proNGF effects. NGF and proNGF are thought to interact with p75NTR or p75NTR-containing complexes, and in this study, the researchers observed a high level of p75NTR in CSCs. The group assessed tumors derived from NGF or proNGF pre‐treated breast cancer cells derived from the first generation of tumorspheres. Interestingly, pretreated cells generated tumors which developed quicker, grew faster, and metastasized more than untreated cells.
The authors provide the first evidence that suggests a critical role for NGF/p75NTR/proNGF in the regulation of breast CSC, and that NGF primes molecular changes that lead to EMT. This provides multiple targets for the generation of an effective anti-tumor therapy targeted at CSCs.