Abstract
BackgroundMounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm.Methodology/Principal FindingsBy integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies.Conclusions/SignificanceOur results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis.
Highlights
Despite progress in both knowledge and treatment, breast cancer remains the major cause of morbidity and mortality in Western Countries [1]
Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm of both resistance to therapy and tumor recurrence
Different lines of evidence converged toward the notion that breast tumors have a mesenchymal ‘‘heart.’’ for decades the major efforts in the fight against breast cancer have searched for diagnostic parameters and therapeutic targets directly or indirectly related to the epithelial phenotype, such as HER-2, estrogen receptors, progesterone receptors, anatomical architecture of the gland, and ductal or luminal morphology
Summary
Despite progress in both knowledge and treatment, breast cancer remains the major cause of morbidity and mortality in Western Countries [1]. The spontaneous development of mesenchymal tumors after epithelial cell regression has been proposed as a model of tumor recurrence [9]. This evidence demonstrates that the capacity to generate mesenchymal tumor cells is inherent in carcinomas, and suggests they could spontaneously evolve into mesenchymal tumors if the epithelium is attacked. Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. The mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
