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Interactions between cancer stem cells and their niche govern metastatic colonization 总被引:1,自引:0,他引:1
Malanchi I Santamaria-Martínez A Susanto E Peng H Lehr HA Delaloye JF Huelsken J 《Nature》2012,481(7379):85-89
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. 相似文献
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Approximately 10 million m3 x s(-1) of water flow from the Pacific Ocean into the Indian Ocean through the Indonesian seas. Within the Makassar Strait, the primary pathway of the flow, the Indonesian throughflow is far cooler than estimated earlier, as pointed out recently on the basis of ocean current and temperature measurements. Here we analyse ocean current and stratification data along with satellite-derived wind measurements, and find that during the boreal winter monsoon, the wind drives buoyant, low-salinity Java Sea surface water into the southern Makassar Strait, creating a northward pressure gradient in the surface layer of the strait. This surface layer 'freshwater plug' inhibits the warm surface water from the Pacific Ocean from flowing southward into the Indian Ocean, leading to a cooler Indian Ocean sea surface, which in turn may weaken the Asian monsoon. The summer wind reversal eliminates the obstructing pressure gradient, by transferring more-saline Banda Sea surface water into the southern Makassar Strait. The coupling of the southeast Asian freshwater budget to the Pacific and Indian Ocean surface temperatures by the proposed mechanism may represent an important negative feedback within the climate system. 相似文献
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Hairus Abdullah Chi-Ning Hsu Hardy Shuwanto Noto Susanto Gultom Worku Lakew Kebede Chang-Mou Wu Chiu-Chun Lai Ri-Ichi Murakami Masayuki Hirota Antonio Norio Nakagaito Dong-Hau Kuo 《自然科学进展(英文版)》2021,31(3):404-413
Relatively small amounts of In-doped Mo(O,S)2 (IMS) catalysts (10%, 20%, and 30%) were deposited on cellulose nanofiber (CNF) by cross-linking them with functional groups of siloxane and epoxy to form CNF-IMS hybrid composites. The as-prepared hybrid composites were characterized and tested their performances toward the photo degradations of cationic (MB and RhB) and anionic (MO) dyes. As indium was doped into Mo(O,S)2 lattice to form solid-solution, the charge transfer and photocarrier separation during the catalytic reaction were simultaneously enhanced as probed with electrochemical impedance spectroscopy and photoluminescence measurements, respectively. To ensure the catalyst on CNF was well deposited and recyclable, the hybrid composite was evaluated with a reusability experiment to show the stability performance in degrading organic dyes. It was found the environmentally friendly CNF-IMS hybrid composite was relatively stable during the reusability experiment, indicating no catalyst powder was leached out during the photocatalytic reaction. The photoreaction mechanism was convinced by radical-scavenging experiments to show that hydroxyl and superoxide played essential roles for the organic dye degradations in visible-light illuminated conditions. The cross-linked organic/inorganic hybrid catalyst showed a prospective visible light active material not only to solve the environmental issue due to the leaching of nanoparticles but also to lower the post-treatment/recycling cost of photocatalyst in industrial application. 相似文献
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