Isolation and characterisation of mouse mammary stem and progenitor cells

我们发现了一种罕见的成体干细胞，所有的乳腺上皮组织都是由它形成的。研究发现，单个干细胞能够在乳房中产生各种类型的细胞，包括产生乳汁的分泌单位和将乳汁输送到乳头的导管细胞。这些细胞类型是大多数人类乳腺肿瘤的原因。然而，癌症最终发展的确切“起源细胞”尚不清楚。我们最近还发现，干细胞群体在至少一种乳腺肿瘤模型中扩增，这表明一些肿瘤可能来自乳腺干细胞本身。使用小鼠模型和细胞测定，我们的目标是首次阐明乳腺中干细胞、祖细胞（“子细胞”）和成熟细胞的层次结构。这些研究将深入了解引起不同类型乳腺癌的各种细胞类型。癌症生物学中一个重要的不断发展的概念是，肿瘤中存在一种罕见的细胞群，称为“癌症干细胞”，具有无限的生长潜力并驱动肿瘤生长。这些细胞甚至可以解释对传统抗癌治疗的抵抗力，因为具有干细胞样特性的细胞能够广泛增殖并形成新的肿瘤。我们将应用我们对正常乳腺干细胞的了解来确定癌症干细胞是否确实存在于小鼠肿瘤中。这些发现将与人类乳腺癌直接相关。然而，我们希望确定特定的细胞表面蛋白的干细胞和前体细胞，可以提供治疗目标。我们的研究将为乳腺癌的细胞类型提供新的见解，以及如何通过改变基因表达来改变它们的命运和肿瘤形成能力。对癌症易感细胞和癌症干细胞的描述可以揭示新的标志物，并为靶向乳腺癌提供新的治疗策略。

We have discovered the rare adult stem cell from which all breast epithelial tissue is formed. A single stem cell was found to be capable of giving rise to various cell types in the breast, including the secretory units that produce milk and the ductal cells that transmit milk to the nipple. These cell types are responsible for the majority of human breast tumours. However, the precise 'cell of origin' from which cancers ultimately develop is not known. We recently also found that the stem cell population is expanded in at least one model of mammary tumours, suggesting that some tumours may arise from the breast stem cell itself. Using mouse models and cellular assays, our aim is to characterise, for the first time, the hierarchy of stem, progenitor ('daughter cells') and mature cells in the mammary gland. These studies will provide insight into the various cell types that give rise to different types of breast cancer. An important evolving concept in cancer biology is that a rare population of cells resident within a tumour, termed 'cancer stem cells', have indefinite growth potential and drive tumour growth. These cells could even account for resistance to conventional anti-cancer treatment, as cells with stem cell-like properties would be able to proliferate extensively and form new tumours. We will apply our knowledge of normal mammary stem cells to determine whether cancer stem cells are indeed present in mouse tumours. Those findings will have direct relevance to human breast cancer. Utlimately, we wish to identify specific cell surface proteins on stem and precursor cells that could provide therapeutic targets. Our studies will provide new insights into the cell types from which breast cancer arise, and how their fate and tumour-forming capacity can be modified by altering gene expression. Delineation of cancer-prone cells and cancer stem cells could reveal new markers and provide new therapeutic strategies to target breast cancer.