Role of Transporters in the Tumor-Stroma Interaction

MMPs in fibroblasts and cancer cells [169]. There are indications that transporters may be regulated by factors originating from the microenvironment [170]. 

However, very little is known about the regulation of transporters. Thus, the chemosensitivity and chemoresistance for a given carrier-mediated chemotherapeutic drug may be influenced by the microenvironment and may change significantly during EMT. This aspect has never been addressed so far. 

CDX2 plays a crucial role in the differentiation of healthy intestinal absorptive cells [173,174]. Clearly, in tumor development, the expression and activity of CDX2 are affected over time [173]. However, opinions about whether CDX2 expression is lost completely or is only in a subset of poorly differentiated tumor cells differ. The mechanisms involved are still subject of ongoing research [173]. Witek et al. even suggested that in 80% of the tumors they analyzed the expression of CDX2 was increased [175]. 

In conclusion, various studies indicate that transporters could be exploited in solid tumors when targeting tumor-initiating cells. However, there is still a significant lack of information available regarding their expression and role in these cells. In addition, to date it is still unclear which models may be most appropriate when studying these aspects in such cells. Thus, for the design of new drugs, medical 

---