TY - JOUR
T1 - Co-opting macrophage traits in cancer progression
T2 - a consequence of tumor cell fusion?
AU - Pawelek, John
AU - Chakraborty, Ashok
AU - Lazova, Rossita
AU - Yilmaz, Yesim
AU - Cooper, Dennis
AU - Brash, Douglas
AU - Handerson, Tamara
PY - 2006
Y1 - 2006
N2 - Tumor-associated macrophages (TAMs) play multiple roles in tumor initiation and progression. Tumors frequently appear in areas of chronic inflammation. This is likely aided by the mutagenic actions of macrophages. Tumor growth and progression is supported by macrophage-induced neoangiogenesis and stroma production, and macrophages produce tumor-stimulating growth factors. In most cancers a high density of TAMs predicts poor outcome. But not only do cancer cells depend upon macrophages for growth and invasion, they also co-opt macrophage traits. These include a wide diversity of molecules and pathways regulating adhesion, matrix alterations, neoangiogenesis, motility, chemotaxis, immune signaling pathways and even multidrug resistance proteins. Evidence is presented that these traits could be generated through macrophage-tumor cell fusion. Fusion has been reported in numerous animal tumor models and was recently documented in 2 human cases. Fusion could also account for the high degree of aneuploidy and plasticity in cancer, and for immune evasion. One common trait of myeloid-tumor fusion is the high expression of Beta1,6-branched N-glycans, used by macrophages in systemic migration. Beta1,6-branched oligosaccharides have long been associated with metastasis in animal models and were recently found to be common in a wide diversity of human cancers. We suggest that Beta1,6-branched oligosaccharides in human cancer may reflect widespread tumor cell fusion. Viewing the cancer cell as a myeloid hybrid provides new approaches towards understanding and treating this complex disease.
AB - Tumor-associated macrophages (TAMs) play multiple roles in tumor initiation and progression. Tumors frequently appear in areas of chronic inflammation. This is likely aided by the mutagenic actions of macrophages. Tumor growth and progression is supported by macrophage-induced neoangiogenesis and stroma production, and macrophages produce tumor-stimulating growth factors. In most cancers a high density of TAMs predicts poor outcome. But not only do cancer cells depend upon macrophages for growth and invasion, they also co-opt macrophage traits. These include a wide diversity of molecules and pathways regulating adhesion, matrix alterations, neoangiogenesis, motility, chemotaxis, immune signaling pathways and even multidrug resistance proteins. Evidence is presented that these traits could be generated through macrophage-tumor cell fusion. Fusion has been reported in numerous animal tumor models and was recently documented in 2 human cases. Fusion could also account for the high degree of aneuploidy and plasticity in cancer, and for immune evasion. One common trait of myeloid-tumor fusion is the high expression of Beta1,6-branched N-glycans, used by macrophages in systemic migration. Beta1,6-branched oligosaccharides have long been associated with metastasis in animal models and were recently found to be common in a wide diversity of human cancers. We suggest that Beta1,6-branched oligosaccharides in human cancer may reflect widespread tumor cell fusion. Viewing the cancer cell as a myeloid hybrid provides new approaches towards understanding and treating this complex disease.
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U2 - 10.1159/000092970
DO - 10.1159/000092970
M3 - Review article
C2 - 16627963
AN - SCOPUS:33646705557
SN - 1420-9519
VL - 13
SP - 138
EP - 155
JO - Contributions to microbiology
JF - Contributions to microbiology
ER -