| Autor: |
Giyong Jang, Jaeik Oh, Eunsung Jun, Jieun Lee, Jee Young Kwon, Jaesang Kim, Sang-Hyuk Lee, Song Cheol Kim, Sung-Yup Cho, Charles Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
npj Genomic Medicine, Vol 7, Iss 1, Pp 1-17 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2056-7944 |
| DOI: |
10.1038/s41525-022-00333-w |
| Popis: |
Abstract Pancreatic cancer exhibits a characteristic tumor microenvironment (TME) due to enhanced fibrosis and hypoxia and is particularly resistant to conventional chemotherapy. However, the molecular mechanisms underlying TME-associated treatment resistance in pancreatic cancer are not fully understood. Here, we developed an in vitro TME mimic system comprising pancreatic cancer cells, fibroblasts and immune cells, and a stress condition, including hypoxia and gemcitabine. Cells with high viability under stress showed evidence of increased direct cell-to-cell transfer of biomolecules. The resulting derivative cells (CD44 high/SLC16A1 high) were similar to cancer stem cell-like-cells (CSCs) with enhanced anchorage-independent growth or invasiveness and acquired metabolic reprogramming. Furthermore, CD24 was a determinant for transition between the tumorsphere formation or invasive properties. Pancreatic cancer patients with CD44 low/SLC16A1 low expression exhibited better prognoses compared to other groups. Our results suggest that crosstalk via direct cell-to-cell transfer of cellular components foster chemotherapy-induced tumor evolution and that targeting of CD44 and MCT1(encoded by SLC16A1) may be useful strategy to prevent recurrence of gemcitabine-exposed pancreatic cancers. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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