Abstract 5358: Comparison of tumor-forming ability in different fractions of pancreatic ductal adenocarcinoma cells

Abstract

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is associated with a high mortality rate due to its aggressive growth and high metastatic rate. Recently, cancer stem cells have been reported to play a central role in the proliferation, metastasis, and drug resistance of cancer. Although cancer stem cell-like cells seem to be included very loosely in cancer cells, information is still limited. Furthermore, the appropriate way of detecting cancer stem cells has remained controversial. In the present study, we tried to detect and collect a side population (SP) fraction as pancreatic cancer stem cells using Hoechst staining, and compared the in vivo tumor-forming abilities between the major population (MP) and SP of PDAC cells. Methods: A human pancreatic cancer cell line, KLM-1, was stained with Hoechst 33342. We distinguished between MP and SP of cells by the positivity of Hoechst, and then each fraction was isolated using a flow cytometer. Different numbers (1.0×102, 103, 104, and 105) and fractions (MP and SP) of cells were subcutaneously injected into the left and right sides of the back of NOD.CB17-Prkdcscid/J (NOD/SCID) mice. During a 5-week test period, the tumor size was measured regularly. Results: After 5 weeks, tumors were formed in mice injected with above 1.0×104 cells of both fractions. Especially, with the injection of 1.0×105 cells, the tumor-forming rate was 100% in the SP group, whereas it was 66.7% in the MP group. Furthermore, tumors were generated at about 1 week after the injection of the SP fraction (1.0×105 cells); however, in the MP group, it took about 3 weeks to generate a tumor after the injection of the same number of cells. Totally, the tumor volumes of the SP group were bigger than those of the MP group. Even with the injection of 1.0×104 cells of the SP fraction, the tumor volume was bigger than that on the injection of 1.0×105 cells of the MP fraction. Subcutaneous tumor tissues derived from SP and MP cells showed similar histological features. Conclusion: The malignancy of the SP fraction in PDAC cells was confirmed. This fraction might include cancer stem like-cell properties, and may be a candidate for therapeutic target in malignant PDAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5358. doi:1538-7445.AM2012-5358