History of Cancer Stem Cells

Abstract

It has been hypothesized for over 40 years that cancers contain the same cell populations as normal tissues: stem cells, proliferating transit-amplifying cells, and terminally differentiated (mature cells). The properties of cancer stem cells include the ability to transplant the tumor, the ability to grow in vitro and the ability to resist conventional therapies. The idea that cancer arose from stem cells dates back to the middle of the 1800s as the embryonal rest theory of cancer. Studies on cancers of germinal cells (tera-tocarcinomas) beginning about 50 years ago established that cancers arise from stem cells and that cancers contain stem cells. For some time teratocarcinomas were believed to be different from other cancers in regard to their origin from stem cells. However, studies on liver cancer, believed to arise from dedifferentiation of mature hepatocytes, revealed that liver cancers also arose from stem cells. More recently cancers of the blood cells (leukemias) were demonstrated to be due to specific blocks to differentiation caused by genetic lesions that allow the leukemic transit-amplifying cells to continue to proliferate and not die (maturation arrest). Conventional chemotherapy, radiotherapy and anti-angiogenic therapies act on the cancer transit-amplifying cells. When these therapies are discontinued the cancer will reform from the therapy resistant cancer stem cells. Re-appreciation of the properties of cancer stem cells allows new directions in differentiation therapy of cancer stem cells by blocking the signals that maintain stemness and allowing the cancer stem cells to differentiate. The goal of this chapter is to introduce the subject of cancer stem cells and present a history of how this concept developed. Two major concepts will be covered: (1) cancers contain stem cells (cancer stem cells); and (2) cancers arise from stem cells. The first concept has significance in designing new stem cell directed therapy for cancer; the second concept is important for directing approaches to prevent cancer.