Davis Samantha J, Divi Vasu, Owen John H, Bradford Carol R, Carey Thomas E, Papagerakis Silvana, Prince Mark E P
Department of Otolaryngology-Head & Neck Surgery, University of Michigan, 1500 E Medical Center Dr, 1903 Taubman Center, SPC 5312, Ann Arbor, MI 48109, USA.
Arch Otolaryngol Head Neck Surg. 2010 Dec;136(12):1260-6. doi: 10.1001/archoto.2010.219.
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.
设计转移的体外和体内模型,以研究头颈部鳞状细胞癌(HNSCC)中癌症干细胞(CSCs)的行为。
使用流式细胞术对细胞进行CD44表达分选。分选后的细胞用于体外侵袭试验。对于体内研究,将CSCs和非CSCs注入小鼠尾静脉,然后采集肺组织或对肺进行成像以评估病变情况。
在体外,CD44(高表达)细胞比CD44(低表达)细胞更具运动性,但侵袭性并不更强。在体内,注射CD44(高表达)细胞的17只小鼠中有8只出现肺部病变,而注射CD44(低表达)细胞的17只小鼠中无一出现肺部病变。其中2个病变源自原发性肿瘤的CSCs,6个源自HNSCC细胞系的CSCs。
在体外,CSCs穿过基底膜的侵袭能力并未增强,但它们能更有效地穿过多孔屏障迁移。相比之下,CSCs在体内能有效地形成肺部病变,而非CSCs不会引发任何远处疾病。这种现象可能是由于CSCs迁移能力增强,这在体内可能比基底膜降解更重要。