The invention relates to a method for the isolation of prostate stem cells, typically prostate cancer stem cells; stem cells and cancer stem cells isolated by the method and their use.
The prostate gland is the major accessory organ of the male reproductive tract, and is the most common site of neoplastic disorders in men. The two main pathologies of the gland are: (i) benign prostatic hyperplasia, which is a non-malignant condition that is common with age and (ii) carcinoma, which is the second most common cause of death in European men, after lung cancer and is increasingly prevalent in our ageing Western Society. Symptoms include, blood in the semen or the urine, frequent pain or stiffness in the lower back, hips or upper thigh. Prostate tumours may be primary (i.e. located in the organ of origin) or secondary (i.e. tumours which form in other organs due to the ability of cancerous cells to move and invade other tissues via the circulatory system).
Prostate cancer can be relatively harmless or extremely aggressive. Some prostate tumours are slow growing and cause few clinical symptoms. Aggressive prostate tumours spread rapidly to the lymph nodes and other organs, especially bone. It is known that the growth of prostate cancer can be inhibited by blocking the supply of male hormones such as testosterone. However, prostate cancers eventually develop and become independent of male sex hormones (i.e. they become androgen-independent prostate cancer cells). These cells are linked with aggressive, malignant prostate cancer. All male mammals have a prostate gland but only humans and dogs are known to naturally develop prostate cancer.
Metastatic prostate cancers predominantly move to the bone and are treated by reducing the production of androgens by blocking androgen production by the adrenal glands and testis. This treatment is only effective for a short period of time as the metastatic lesions become androgen independent and grow uncontrollably.
The presence of androgen independent prostate cancer cells means that this treatment regime is no longer effective and further intervention is required to control the progress of the disease. A similar response is seen to chemotherapeutic and radiotherapy treatments. As a result, metastatic prostate cancer remains an incurable disease by current treatment strategies. There is therefore a continual need to identify new therapeutic targets to provide new treatments for prostate cancer.
A problem underlying the effective treatment of cancerous conditions is the identification of a population of cells in a tumour that have the ability of sustaining the growth of a tumour. The evidence suggests that tumours are clonal and are therefore derived from a single cell. However, there are few studies that identify and characterise those cells types that are responsible for maintaining tumour cell growth. Some have searched for these so called "cancer stem cells".
We have identified CD133, which is expressed by primitive haematopoietic stem cells and developing epithelia as a further stem cell marker for prostate epithelia. CD133 cells are restricted to the α2β1 integrin expressing population (the receptor for type I collagen) and are located in the basal layer, often at the base of a budding region or branching point. α2β1 integrin/CD133+ cells exhibit two important attributes of epithelial stem cells: they possess a high in vitro proliferative potential and can reconstitute prostatic-like acini in immunocompromised male nude mice.
Prostate tumour stem cells have been directly isolated from lymph node and prostate glands from a series of patient samples using the following markers: human epithelial antigen (HEA), CD44 (which is expressed by basal cells in the prostate; Liu et al., 1997), α2β1 integrin and CD133. Morphologically the cells range from fibroblastoid (expressing high levels of vimentin which is typical of transformed cells) or epithelial, and are capable of producing progenitors associated with prostate epithelial differentiation. Invasion assays, using Matrigel-coated filters have determined that these cells have a similar capacity to invade through Matrigel than PC3M (a highly metastatic subline of PC3 cells.
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Last Updated Sep 2014