Microenvironmental regulation of metastasis

Microenvironmental regulation of metastasis

2009 April ; 9(4): 239–252 | Johanna A. Joyce and Jeffrey W. Pollard
Metastasis is a complex process involving multiple stages, including escape from the primary tumor, survival in the circulation, seeding at distant sites, and growth. The microenvironment, particularly bone marrow-derived cells (BMDCs), plays a crucial role in each of these stages. BMDCs, including macrophages, neutrophils, and mast cells, are recruited to tumors and enhance cancer cell survival, growth, invasion, and dissemination. Chronic inflammation and the presence of BMDCs can promote tumor progression by modulating the extracellular matrix (ECM) and facilitating interactions between different cell types. Macrophages, in particular, have been shown to promote tumor angiogenesis, invasion, intravasation, and metastasis through paracrine loops involving factors like epidermal growth factor (EGF) and colony-stimulating factor 1 (CSF1). Myeloid-derived suppressor cells (MDSCs) and mesenchymal stem cells (MSCs) also contribute to tumor progression by suppressing the immune response and modulating cancer cell behavior. The microenvironment at metastatic sites further influences the survival and growth of metastatic cells, with factors like chemokines and integrins playing key roles in adhesion and invasion. The establishment of pre-metastatic niches, created by primary tumors, can enhance metastasis by recruiting BMDCs and providing a supportive environment for metastatic cells. Despite the importance of the microenvironment, the molecular mechanisms underlying these processes remain largely unknown, and therapeutic targeting of these factors is an area of active research.Metastasis is a complex process involving multiple stages, including escape from the primary tumor, survival in the circulation, seeding at distant sites, and growth. The microenvironment, particularly bone marrow-derived cells (BMDCs), plays a crucial role in each of these stages. BMDCs, including macrophages, neutrophils, and mast cells, are recruited to tumors and enhance cancer cell survival, growth, invasion, and dissemination. Chronic inflammation and the presence of BMDCs can promote tumor progression by modulating the extracellular matrix (ECM) and facilitating interactions between different cell types. Macrophages, in particular, have been shown to promote tumor angiogenesis, invasion, intravasation, and metastasis through paracrine loops involving factors like epidermal growth factor (EGF) and colony-stimulating factor 1 (CSF1). Myeloid-derived suppressor cells (MDSCs) and mesenchymal stem cells (MSCs) also contribute to tumor progression by suppressing the immune response and modulating cancer cell behavior. The microenvironment at metastatic sites further influences the survival and growth of metastatic cells, with factors like chemokines and integrins playing key roles in adhesion and invasion. The establishment of pre-metastatic niches, created by primary tumors, can enhance metastasis by recruiting BMDCs and providing a supportive environment for metastatic cells. Despite the importance of the microenvironment, the molecular mechanisms underlying these processes remain largely unknown, and therapeutic targeting of these factors is an area of active research.
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