Cancer stem cells: implications for the progression and treatment of metastatic disease
Tóm tắt
Introduction The metastatic process The cancer stem cell hypothesis Parallels between stem cell behaviour and metastatic behaviour Therapeutic implications Conclusions and future directions
Metastasis is the major cause of death for cancer patients with solid tumours, due mainly to the ineffectiveness of current therapies once metastases begin to form. Further insight into the biology of metastasis is therefore essential in order to gain a greater understanding of this process and ultimately to develop better cancer therapies. Metastasis is an inefficient process, such that very few cells that leave a tumour successfully form macrometastases in distant sites. This suggests that only a small subset of cells can successfully navigate the metastatic cascade and eventually re‐initiate tumour growth to form life‐threatening metastases. Recently, there has been growing support for the cancer stem cell (CSC) hypothesis which stipulates that primary tumours are initiated and maintained by a small subpopulation of cancer cells that possess “stem‐like” characteristics. Classical properties of normal stem cells are strikingly reminiscent of the observed experimental and clinical behaviour of metastatic cancer cells, including an unlimited capacity for self renewal; the requirement for a specific ‘niche’or microenvironment to grow; use of the stromal cell‐derived factor 1 (SDF‐1)/chemokine receptor 4 (CXCR4) axis for migration; enhanced resistance to apoptosis and an increased capacity for drug resistance. Therefore, in addition to playing a role in primary tumour formation, we believe that CSCs are also key players in the metastatic process. We will review the current evidence supporting this idea and discuss the potential implications of the CSC hypothesis with regards to experimental investigation and treatment of metastatic disease.
Từ khóa
Tài liệu tham khảo
Canadian Cancer Statistics2007.http://www.cancer.ca
Ewing J, 1928, Neoplastic Diseases, 77
Paget S, 1989, The distribution of secondary growths in cancer of the breast (re‐publication of the original 1889 Lancet article), Cancer Met Rev, 8, 98
Virchow R, 1855, Editorial, Virchows Arch Pathol Anat Physiol Klin Med, 3, 23
Allan AL, 2007, Tumor dormancy and cancer stem cells: implications for the biology and treatment of breast cancer metastasis, Breast Dis, 26, 87, 10.3233/BD-2007-26108
Kucia M, 2006, Stem cells as a two edged sword – from regeneration to tumor formation, J Physiol Pharmacol, 57, 5
Scadden DT, 2007, The stem cell niche in health and leukemic disease, Clin Hematol, 20, 19
Hendrix MJC, 2007, Reprogramming metastatic tumor cells with embryonic microenvironments, Nature, 7, 246
Wang W, 2007, The cofilin pathway in breast cancer invasion and metastasis, Nature, 7, 429
Kim M, 2002, The mul‐tidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells, Clin Cancer Res, 8, 22
Slack JL, 2000, Molecular analysis and clinical outcome of adult APL patients with the type V PML‐RARalpha isoform: results from intergroup protocol 0129, Blood, 95, 398