Stem cells, therapy resistance and metastasis in colorectal cancer
Institute for Research in Biomedicine (IRB Barcelona)
The Cancer Stem Cell (CSC) concept states that tumor growth, analogous to renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It provides attractive explanations for the clinical behavior of cancers and inspires treatment strategies that specifically target CSCs, the 'beating heart' of the tumor. Over the past years, an avalanche of studies has identified CSCs by expression of individual marker genes but the nature and features of these cells remain largely uncharacterized. As a case of example, LGR5 has been established as a bonafide marker of CSCs in gastrointestinal tumors. Many CRCs contain abundant LGR5+ cells yet clonal analysis suggests that only a small proportion of these cells function as CSCs. It is also known that many CRCs contain few or no LGR5+ cells, yet these tumors may still exhibit a hierarchical organization. Here, I will discuss our recent work on the functional states adopted by LGR5+ cells during CRC progression and the role of this cell population in chemotherapy resistance and metastatic dissemination.