Subpopulations of cancer stem cells found in papillary thyroid carcinoma

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2017.12.017· OSTI ID:23082489

Mirshahidi, Saied ^[1]; Simental, Alfred; Lee, Steve C.; De Andrade Filho, Pedro A.; Peterson, Nathaniel R.; Cao, Wenlong ^[2]; Necochea-Campion, Rosalia de ^[1]; Yang, Hao ^[3]; Duerksen-Hughes, Penelope ^[4]; Yuan, Xiangpeng ^[2]

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1. Cancer Center Biospecimen Laboratory, Loma Linda University Medical Center, Loma Linda, CA 92354 (United States)
2. Department of Otolaryngology-Head and Neck Surgery, Loma Linda University Medical Center, Loma Linda, CA 92354 (United States)
3. Shaanxi Spine Medicine Research Center, Hong Hui Hospital, Xi'an Jiaotong University, Shaanxi 710054 (China)
4. Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92354 (United States)

Highlights: • Papillary thyroid carcinoma primary cell culture derived spheres behave as cancer stem cells. • Depletion of ALDH{sup +} sphere cells does not eradicate papillary thyroid carcinoma. • ALDH{sup -} sphere cells can also function independently as thyroid carcinoma cancer stem cells. • ALDH{sup -} and ALDH{sup +} sphere cells coordinate in thyroid cancer initiation and progression. • Targeting both ALDH{sup +} and ALDH{sup -} cancer stem cells may effectively treat thyroid cancer. Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer and while it has a generally good prognosis, tumor recurrence remains a major clinical challenge. Studying laboratory cell lines as well as clinical specimens indicate that PTC may follow the cancer stem cell (CSC) model. However, CSC characteristics relevant in PTC initiation and progression remain largely unknown. Here we studied a population of sphere-growing tumor cells isolated from primary cultures of clinical PTC. These sphere-growing cells consisted of aldehyde dehydrogenase positive (ALDH{sup +}) and ALDH negative (ALDH{sup -}) cell subpopulations and demonstrated a hierarchical pattern of cell division. Using combinations of selective depletion, specific inhibition and cell sorting, we found that both subpopulations of the sphere cells were able to self-renew and initiate xenograft tumors independently, and fulfilled the definition of CSC. Importantly, when the subpopulations functioned together, the cancer-initiation efficiency and the xenograft tumor progression were significantly enhanced compared to either subpopulation alone. These data revealed crucial roles of ALDH{sup -} CSC in PTC biology and suggested that CSC subpopulations function cooperatively to control PTC initiation and progression. Together, our study indicates that CSC subpopulations isolated from clinical specimens offer unprecedented opportunities for investigating PTC pathogenesis and developing effective therapies.

• OSTI ID: 23082489
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 362; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOMAS
CELL CULTURES
CELL DIVISION
OXIDOREDUCTASES
STEM CELLS
THYROID
TUMOR CELLS