Pancreatic Cancer Stem-Like Cells With High Calreticulin Expression Associated With Immune Surveillance

具有高钙网蛋白表达的胰腺癌干细胞样细胞与免疫监视相关

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作者:Yasuhiro Fujiwara, Ryouichi Tsunedomi, Kiyoshi Yoshimura, Satoshi Matsukuma, Nobuyuki Fujiwara, Mitsuo Nishiyama, Shinsuke Kanekiyo, Hiroto Matsui, Yoshitaro Shindo, Yukio Tokumitsu, Shin Yoshida, Michihisa Iida, Nobuaki Suzuki, Shigeru Takeda, Tatsuya Ioka, Shoichi Hazama, Hiroaki Nagano

Conclusion

In addition to the cancer stem cell properties, the P-CSLC, which showed elevated CALR expression on the cell surface, might be associated with evasion of immune surveillance.

Methods

PANC-1-Lm cells were obtained as P-CSLCs from a human pancreatic cancer cell line, PANC-1, using a sphere induction medium followed by long-term cultivation on laminin. To examine the cancer stem cell properties, subcutaneous injection of the cells into immune-deficient mice and sphere formation assay were performed. Cell surface expression analysis was performed using flow cytometry.

Objective

Pancreatic cancer stem-like cells (P-CSLCs) are thought to be associated with poor prognosis. Previously, we used proteomic analysis to identify a chaperone pro-phagocytic protein calreticulin (CALR) as a P-CSLC-specific protein. This study aimed to investigate the association between CALR and P-CSLC.

Results

PANC-1-Lm showed an increased proportion of cell surface CALR-positive and side-population fractions compared with parental cells. PANC-1-Lm cells also had higher frequency of xenograft tumor growth and sphere formation than PANC-1 cells. Moreover, sorted CALRhigh cells from PANC-1-Lm had the highest sphere formation frequency among tested cells. Interestingly, the number of programmed death-ligand 1-positive cells among CALRhigh cells was increased as well, whereas that of human leukocyte antigen class I-positive cells decreased.

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