Transforming growth factor β1 contributes to the invasiveness of pancreatic ductal adenocarcinoma cells through the regulation of CD24 expression

Objectives: The aim of this study was to investigate the role of CD24 in the invasiveness of pancreatic ductal adenocarcinoma (PDAC). Methods: We used 2 human PDAC cell lines containing large numbers of CD24-positive (CD24 ⁺) cells (>65%; AsPC-1 cells) or few CD24 ⁺ cells (<20%; CFPAC-1 cells). Invasiveness was estimated using the Matrigel invasion assay. The role of CD24 in invasiveness was evaluated using small interference RNA against CD24 mRNA. Results: The invasive ability of CD24 ⁺ cells collected by cell sorter was higher than that of CD24-negative (CD24 ^-) cells. On the other hand, silencing of CD24 decreased the invasive ability of CD24 ⁺ cells. Importantly, considerable amount of CD24 ⁺ cells was converted to CD24 ^- cells within 24 hours under in vitro culture condition. Transforming growth factor β1 significantly inhibited this conversion and consequently maintained the high invasiveness of CD24 ⁺ cells. Conclusions: Our data show that CD24 contributes to the invasive ability of PDAC and also suggest that transforming growth factor β1 may contribute to the invasiveness of PDAC by suppressing the conversion from CD24 ⁺ cells to CD24 ^- cells at the tumor site.