Abstract
3986
The cancer stem cell hypothesis suggests that only a rare population of cells comprising the tumor have stem cell-like properties, defined by self-renewal and proliferative capacity, which are responsible for growth and progression of the tumor. We report the identification of a small population of cells in small cell lung cancer (SCLC) that possess tumor progenitor-like properties. We demonstrate that these cells express high levels of urokinase plasminogen activator receptor (uPAR/CD87), a gene known to contribute to development of the most invasive phenotypes in several cancers, e.g. ovarian, prostate and brain. These CD87+ cells display high clonogenic potential in in vitro assays and are able to generate a heterogeneous cell population similar to the parental cell line both in vitro and in vivo. In order to study human tumor growth and dissemination, we used a mouse model in which SCID mice were engrafted with human fetal lung tissue under the kidney capsule. Primary and metastatic SCLC cells were injected into the human fetal lung xenograft. Importantly, 2 month after the injection of SCLC cells, distant metastasis were detected in the host mouse lung and liver, while spleen, kidney and brain of the host remained intact. The metastatic human SCLC cells expressed high levels of uPAR/CD87, suggesting that CD87+ cells responsible for tumor progression. The identification of lung cancer progenitor cells will provide insight into human lung cancer pathogenesis and may establish new targets for anticancer therapies.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]