Pancreatic Cancer Stem-Like Cells With High Calreticulin Expression Associated With Immune Surveillance. Issue 3 (March 2021)

• Record Type: Journal Article
• Authors: Fujiwara, Yasuhiro; Tsunedomi, Ryouichi; Yoshimura, Kiyoshi; Matsukuma, Satoshi; Fujiwara, Nobuyuki; Nishiyama, Mitsuo; Kanekiyo, Shinsuke; Matsui, Hiroto; Shindo, Yoshitaro; Tokumitsu, Yukio; Yoshida, Shin; Iida, Michihisa; Suzuki, Nobuaki; Takeda, Shigeru; Ioka, Tatsuya; Hazama, Shoichi; Nagano, Hiroaki
• Is Part Of: Pancreas. Volume 50:Issue 3(2021)
• Publication Date: 2021-03
• Subjects: pancreatic cancer -- cancer stem cell -- calreticulin -- immune surveillance -- cell surface; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000001772
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : 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. 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. 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 CALR high 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 CALR high cells was increased as well, whereas that of human leukocyte antigen class I–positive cells decreased. 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.