Metastatic potential of cancer stem cells in head and neck squamous cell carcinoma.
ABSTRACT to design in vitro and in vivo models of metastasis to study the behavior of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC).
cells were sorted for CD44 expression using flow cytometry. Sorted cells were used in an in vitro invasion assay. For in vivo studies, CSCs and non-CSCs were injected into the tail veins of mice, and lungs were either harvested or imaged to evaluate for lesions.
in vitro, CD44(high) cells were more motile but not more invasive than CD44(low) cells. In vivo, 8 of 17 mice injected with CD44(high) cells and 0 of 17 mice injected with CD44(low) cells developed lung lesions. Two of the lesions arose from CSCs from a primary tumor and 6 from CSCs from HNSCC cell lines.
in vitro, CSCs do not have an increased ability to invade through basement membrane, but they migrate more efficiently through a porous barrier. In contrast, CSCs efficiently formed lung lesions in vivo, whereas non-CSCs did not give rise to any distant disease. This phenomenon could be due to the enhanced migratory capacity of CSCs, which may be more important than basement membrane degradation in vivo.
Article: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma.[show abstract] [hide abstract]
ABSTRACT: Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC) contains a heterogeneous population of cancer cells. We developed an immunodeficient mouse model to test the tumorigenic potential of different populations of cancer cells derived from primary, unmanipulated human HNSCC samples. We show that a minority population of CD44(+) cancer cells, which typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the CD44(+) cancer cells have a primitive cellular morphology and costain with the basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble differentiated squamous epithelium and express the differentiation marker Involucrin. The tumors that arose from purified CD44(+) cells reproduced the original tumor heterogeneity and could be serially passaged, thus demonstrating the two defining properties of stem cells: ability to self-renew and to differentiate. Furthermore, the tumorigenic CD44(+) cells differentially express the BMI1 gene, at both the RNA and protein levels. By immunohistochemical analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to play a role in self-renewal in other stem cell types and to be involved in tumorigenesis. Taken together, these data demonstrate that cells within the CD44(+) population of human HNSCC possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation and form unique histological microdomains that may aid in cancer diagnosis.Proceedings of the National Academy of Sciences 02/2007; 104(3):973-8. · 9.68 Impact Factor