Interactions between cancer stem cells and their niche govern metastatic colonization
Autor: | Albert Santamaria-Martínez, Hong Peng, Joerg Huelsken, Jean-François Delaloye, Evelyn Susanto, Ilaria Malanchi, Hans-Anton Lehr |
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Rok vydání: | 2011 |
Předmět: |
Lung Neoplasms
Stromal cell Population Breast Neoplasms Periostin Biology Metastasis Mice Cancer stem cell medicine Animals Neoplasm Metastasis Stem Cell Niche education Wnt Signaling Pathway education.field_of_study Multidisciplinary Cancer medicine.disease Mice Inbred C57BL Cancer cell Immunology Neoplastic Stem Cells Cancer research Female Stromal Cells Stem cell Cell Adhesion Molecules |
Zdroj: | Nature. 481:85-89 |
ISSN: | 1476-4687 0028-0836 |
Popis: | Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps. Although dissemination of tumour cells seems to be an early and frequent event, the successful initiation of metastatic growth, a process termed 'metastatic colonization', is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites. Prevalent target sites are characteristic of many tumour entities, suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease. |
Databáze: | OpenAIRE |
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