Metastatic activity and chemotherapy resistance in human pancreatic cancer—influence of cancer stem cells

Abstract

RESISTANCE TO CHEMOTHERAPY, whether intrinsic or acquired, is believed to be a major cause of treatment failure in pancreatic cancer. Attempts to better understand the molecular basis for these characteristics of pancreatic cancer have focused on studying the gene and protein expression profiles of both resected tumors and pancreatic cancer cell lines. However, many of these types of studies have not taken into account the heterogeneity of cancer cells within a particular tumor or cell line. Emerging evidence has demonstrated that the capacity of a tumor to grow is potentially dependent on a small subset of cells termed ‘‘cancer stem cells.’’ The ‘‘cancer stem cell hypothesis’’ proposes that tumors consist of a cellular hierarchy which reflects the pluripotency of the originally transformed cell. The purported significance of stem cells in cancer development is based on two basic characteristics. First, stem cells are the only longlived cells within tissues and therefore are capable of accumulating multiple transforming mutations. Second, stem cells are able to self-renew into new stem cells with identical potential for proliferation, differentiation, and even mutation. Consequently, cancer stem cells are defined as cancer cells that have the ability to divide into new malignant stem cells and daughter cells that can then