Lung Cancer Stem Cells

Abstract

Two theories describe the development of cancer. The clonal evolution theory posits that cancer arises from a single cell of origin, and hat progression of the cancer occurs due to the acquisition of genetic abnormalities within the original clone, allowing the sequential selection of more and more aggressive sublines; whereas the cancer stem cell theory posits that cancer cells are heterogeneous, and that only the cancer stem cell subset of tumor cells is able to extensively proliferate and metastasize. Stem cells occur normally in human beings. Adult somatic stem cells, lacking sufficient telomerase activity to prevent telomere loss, do not have the capacity to replicate indefinitely. Pluripotent adult somatic stem cells, with their limited ability to self-renew, have been found in many mature tissues, including lung. These cells are thought to be responsible for tissue regeneration and repair. Adult stem cells are believed to localize in their respective tissues in a special microenvironment—the so-called stem cell niche. These adult somatic stem cells are considered to have an increased risk for malignant transformation. The concept of cancer arising from hypothetical rare cells, with the stem cell properties of self-renewal and differentiation into progenitors, that exclusively maintain neoplastic clones—so called cancer stem cells—has already been acknowledged for hematologic malignancies. Many solid tumors are also thought to arise from cancer stem cells; specifically, originating from organ-specific stem cells. The concept of cancer stem cells is based on the principle that, in the multistep process of undergoing malignant transformation, a cell must be able to self-renew in order to accumulate enough mutations to transform into a malignant cell. These cancer stem cells allow for the propagation of cancer cells that retain the primary tumor’s diverse marker profile.